The MYC transcription factor network: balancing metabolism, proliferation and oncogenesis

doi:10.1007/s11684-018-0650-z

Front. Med.

2018, Vol. 12

Issue (4) : 412-425 https://doi.org/10.1007/s11684-018-0650-z

REVIEW

The MYC transcription factor network: balancing metabolism, proliferation and oncogenesis

Patrick A. Carroll, Brian W. Freie, Haritha Mathsyaraja, Robert N. Eisenman(

)

Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 90109, USA

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Abstract

Transcription factor networks have evolved in order to control, coordinate, and separate, the functions of distinct network modules spatially and temporally. In this review we focus on the MYC network (also known as the MAX-MLX Network), a highly conserved super-family of related basic-helix-loop-helix-zipper (bHLHZ) proteins that functions to integrate extracellular and intracellular signals and modulate global gene expression. Importantly the MYC network has been shown to be deeply involved in a broad spectrum of human and other animal cancers. Here we summarize molecular and biological properties of the network modules with emphasis on functional interactions among network members. We suggest that these network interactions serve to modulate growth and metabolism at the transcriptional level in order to balance nutrient demand with supply, to maintain growth homeostasis, and to influence cell fate. Moreover, oncogenic activation of MYC and/or loss of a MYC antagonist, results in an imbalance in the activity of the network as a whole, leading to tumor initiation, progression and maintenance.

Keywords network transcription cancer MYC MAX MLX

Corresponding Author(s): Robert N. Eisenman

Just Accepted Date: 02 July 2018 Online First Date: 27 July 2018 Issue Date: 03 September 2018

Cite this article:

Patrick A. Carroll,Brian W. Freie,Haritha Mathsyaraja, et al. The MYC transcription factor network: balancing metabolism, proliferation and oncogenesis[J]. Front. Med., 2018, 12(4): 412-425.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-018-0650-z
https://academic.hep.com.cn/fmd/EN/Y2018/V12/I4/412

Fig.1 The MYC network showing the three modules from left to right—MYC; MXD/MNT/MGA; and MLXIP/MLXIPL and the dimerization interactions with MAX and/or MLX (indicated by double-headed arrows). The resulting heterodimers bind to E-Box sequences in DNA.

Fig.2 Crystal structures of the bHLHZ domains of (left) MYC-MAX heterodimer (PDB:INKP) and (right) MXD1-MAX heterodimer (PDB:INLW) bound to E-box DNA (5′-CACGTG-3′) at 19 nm and 2 nm resolution, respectively [¹]. Image created with the PyMOL Molecular Graphics System, Version 1.5.0.4, Schrödinger, LLC.

Fig.3 Organization of the MYC, MAX, MNT and MGA proteins. Heterodimers are formed by direct interaction of the basic helix–loop–helix-zipper (bHLH-Z) domain of MAX with the bHLH-Z domains of either MYC, MNT or MGA (blue lines). Number of residues in each protein indicated at C terminus. MYC: MBI-IV — conserved MYC boxes; PEST— region rich in proline, glutamic acid, serine and threonine; NLS— nuclear localization sequence; Calpain cleavage site—proteolytic cleavage to generate MYC-Nick [²]. MNT: SID — binding site for the mSIN3 co-repressor complex. MGA: repression mediated through assembly into a variant polycomb repressor complex (PRC1.6). Question mark indicates that the region of MGA that directly interacts with the complex is unknown. Protein lengths not to scale. See text for details.

Fig.4 Organization of MLXIP (MondoA) and MLX. MLXIP: highly conserved regions proximal to the N terminus are thought to be responsible for binding to glucose metabolites. MLX interacts with MLXIP through their bHLHZ and DCD domains. MLX has 3 isoforms generated by alternative splicing: MLX-g (nuclear localized), MLX-a and MLX-b (both cytoplasmic).

Fig.5 A hypothetical representation of two states of the MYC network and their impact on gene expression programs that influence growth, proliferation, differentiation, apoptosis and metabolism. (A) A balanced network in which gene expression is controlled through normal endogenous regulation of the MYC network. Transcriptional effects of MYC-MAX are balanced by MNT (heterodimerized with either MAX or MLX), MGA-MAX, and, under conditions of stress, by MLXIP-MLX or MLXIPL-MLX. (B) An unbalanced network due to deregulation of MYC expression. In this state MYC-MAX suppresses differentiation, reprograms metabolism, and triggers the apoptotic pathway. The suppressive effects of MGA-MAX and MNT-MAX/MLX on proliferation are overwhelmed by MYC-MAX which contributes to suppression of MYC- induced apoptosis. Increased nuclear accumulation of MLXIP-MLX (in response to deregulated MYC and/or metabolic stress) adjusts metabolic reprogramming by MYC-MAX and further reduces apoptosis. The effects on gene expression are presumed to occur through genomic binding and co-occupancy by network members. Green arrows, transcriptional activation; red arrows, transcriptional repression. Arrow width proportional to estimated transcriptional effect. Diagram adapted from [⁵].

1	Nair SK, Burley SK. X-ray structures of Myc-Max and Mad-Max recognizing DNA. Molecular bases of regulation by proto-oncogenic transcription factors. Cell 2003; 112(2): 193–205 https://doi.org/10.1016/S0092-8674(02)01284-9 pmid: 12553908
2	Conacci-Sorrell M, Ngouenet C, Eisenman RN. Myc-Nick: a cytoplasmic cleavage product of Myc that promotes α-tubulin acetylation and cell differentiation. Cell 2010;142(3):480–493 PMID: 20691906 https://doi.org/10.1016/j.cell.2010.06.037
3	Davidson EH, Rast JP, Oliveri P, Ransick A, Calestani C, Yuh CH, Minokawa T, Amore G, Hinman V, Arenas-Mena C, Otim O, Brown CT, Livi CB, Lee PY, Revilla R, Rust AG, Pan Z, Schilstra MJ, Clarke PJ, Arnone MI, Rowen L, Cameron RA, McClay DR, Hood L, Bolouri H. A genomic regulatory network for development. Science 2002; 295(5560): 1669–1678 https://doi.org/10.1126/science.1069883 pmid: 11872831
4	Newman MEJ. Modularity and community structure in networks. Proc Natl Acad Sci USA 2006; 103(23): 8577–8582 https://doi.org/10.1073/pnas.0601602103 pmid: 16723398
5	Diolaiti D, McFerrin L, Carroll PA, Eisenman RN. Functional interactions among members of the MAX and MLX transcriptional network during oncogenesis. Biochim Biophys Acta 2015; 1849(5): 484–500 https://doi.org/10.1016/j.bbagrm.2014.05.016 pmid: 24857747
6	Patel VR, Eckel-Mahan K, Sassone-Corsi P, Baldi P. CircadiOmics: integrating circadian genomics, transcriptomics, proteomics and metabolomics. Nat Methods 2012; 9(8): 772–773 https://doi.org/10.1038/nmeth.2111 pmid: 22847108
7	Kim J, Chu J, Shen X, Wang J, Orkin SH. An extended transcriptional network for pluripotency of embryonic stem cells. Cell 2008; 132(6): 1049–1061 https://doi.org/10.1016/j.cell.2008.02.039 pmid: 18358816
8	Chronis C, Fiziev P, Papp B, Butz S, Bonora G, Sabri S, Ernst J, Plath K. Cooperative binding of transcription factors orchestrates reprogramming. Cell 2017; 168(3): 442–459.e20 https://doi.org/10.1016/j.cell.2016.12.016 pmid: 28111071
9	Kueh HY, Rothenberg EV. Regulatory gene network circuits underlying T cell development from multipotent progenitors. Wiley Interdiscip Rev Syst Biol Med 2012; 4(1): 79–102 https://doi.org/10.1002/wsbm.162 pmid: 21976153
10	Conacci-Sorrell M, McFerrin L, Eisenman RN. An overview of MYC and its interactome. Cold Spring Harb Perspect Med 2014;4(1):a014357 PMID: 24384812 https://doi.org/10.1101/cshperspect.a014357
11	O’Shea JM, Ayer DE. Coordination of nutrient availability and utilization by MAX- and MLX-centered transcription networks. Cold Spring Harb Perspect Med 2013; 3(9): a014258 https://doi.org/10.1101/cshperspect.a014258 pmid: 24003245
12	Peterson CW, Ayer DE. An extended Myc network contributes to glucose homeostasis in cancer and diabetes. Front Biosci (Landmark Ed) 2011;16:2206–2223 PMID: 21622171
13	Sloan EJ, Ayer DE. Myc, mondo, and metabolism. Genes Cancer 2010; 1(6): 587–596 https://doi.org/10.1177/1947601910377489 pmid: 21113411
14	Blackwood EM, Eisenman RN. Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA binding complex with Myc. Science 1991; 251(4998):1211–1217 PMID: 2006410
15	Billin AN, Eilers AL, Queva C, Ayer DE. Mlx, a novel Max-like BHLHZip protein that interacts with the Max network of transcription factors. J Biol Chem 1999; 274(51): 36344–36350 https://doi.org/10.1074/jbc.274.51.36344 pmid: 10593926
16	Berberich SJ, Cole MD. Casein kinase II inhibits the DNA-binding activity of Max homodimers but not Myc/Max heterodimers. Genes Dev 1992; 6(2): 166–176 https://doi.org/10.1101/gad.6.2.166 pmid: 1737614
17	Meroni G, Cairo S, Merla G, Messali S, Brent R, Ballabio A, Reymond A. Mlx, a new Max-like bHLHZip family member: the center stage of a novel transcription factors regulatory pathway? Oncogene 2000; 19(29): 3266–3277 https://doi.org/10.1038/sj.onc.1203634 pmid: 10918583
18	Hurlin PJ, Quéva C, Eisenman RN. Mnt, a novel Max-interacting protein is coexpressed with Myc in proliferating cells and mediates repression at Myc binding sites. Genes Dev 1997; 11(1): 44–58 https://doi.org/10.1101/gad.11.1.44 pmid: 9000049
19	Ayer DE, Eisenman RN. A switch from Myc:Max to Mad:Max heterocomplexes accompanies monocyte/macrophage differentiation. Genes Dev 1993; 7(11): 2110–2119 https://doi.org/10.1101/gad.7.11.2110 pmid: 8224841
20	Hann SR, Eisenman RN. Proteins encoded by the human c-myc oncogene: differential expression in neoplastic cells. Mol Cell Biol 1984; 4(11): 2486–2497 https://doi.org/10.1128/MCB.4.11.2486 pmid: 6513926
21	Billin AN, Ayer DE. The Mlx network: evidence for a parallel Max-like transcriptional network that regulates energy metabolism. Curr Top Microbiol Immunol 2006; 302: 255–278 https://doi.org/10.1007/3-540-32952-8_10 pmid: 16620032
22	Billin AN, Eilers AL, Coulter KL, Logan JS, Ayer DE. MondoA, a novel basic helix-loop-helix-leucine zipper transcriptional activator that constitutes a positive branch of a max-like network. Mol Cell Biol 2000; 20(23): 8845–8854 https://doi.org/10.1128/MCB.20.23.8845-8854.2000 pmid: 11073985
23	Roussel M, Saule S, Lagrou C, Rommens C, Beug H, Graf T, Stehelin D. Three new types of viral oncogene of cellular origin specific for haematopoietic cell transformation. Nature 1979; 281(5731): 452–455 https://doi.org/10.1038/281452a0 pmid: 226888
24	Sheiness D, Bishop JM. DNA and RNA from uninfected vertebrate cells contain nucleotide sequences related to the putative transforming gene of avian myelocytomatosis virus. J Virol 1979; 31(2): 514–521 pmid: 225569
25	Schaub FX, Dhankani V, Berger AC, Trivedi M, Richardson AB, Shaw R, Zhao W, Zhang X, Ventura A, Liu Y, Ayer DE, Hurlin PJ, Cherniack AD, Eisenman RN, Bernard B, Grandori C; Cancer Genome Atlas Network. Pan-Cancer alterations in MYC oncogene and its proximal network across the cancer genome atlas. Cell Syst 2018; 6: 282–300 https://doi.org/10.1016/j.cels.2018.03.003 pmid: 29596783
26	Meyer N, Penn LZ. Reflecting on 25 years with MYC. Nat Rev Cancer 2008; 8(12):976–990 PMID: 19029958 https://doi.org/10.1038/nrc2231
27	Eilers M, Eisenman RN. Myc’s broad reach. Genes Dev 2008; 22(20): 2755–2766 https://doi.org/10.1101/gad.1712408 pmid: 18923074
28	Armelin HA, Armelin MCS, Kelly K, Stewart T, Leder P, Cochran BH, Stiles CD. Functional role for c-myc in mitogenic response to platelet-derived growth factor. Nature 1984; 310(5979): 655–660 https://doi.org/10.1038/310655a0 pmid: 6088986
29	Kelly K, Cochran BH, Stiles CD, Leder P. Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell 1983; 35(3 Pt 2): 603–610 https://doi.org/10.1016/0092-8674(83)90092-2 pmid: 6606489
30	Wang R, Dillon CP, Shi LZ, Milasta S, Carter R, Finkelstein D, McCormick LL, Fitzgerald P, Chi H, Munger J, Green DR. The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity 2011;35(6):871–882 PMID: 22195744 https://doi.org/10.1016/j.immuni.2011.09.021
31	Gabay M, Li Y, Felsher DW. MYC activation is a hallmark of cancer initiation and maintenance. Cold Spring Harb Perspect Med 2014; 4(6): a014241 https://doi.org/10.1101/cshperspect.a014241 pmid: 24890832
32	Okuyama H, Endo H, Akashika T, Kato K, Inoue M. Downregulation of c-MYC protein levels contributes to cancer cell survival under dual deficiency of oxygen and glucose. Cancer Res 2010; 70(24): 10213–10223 https://doi.org/10.1158/0008-5472.CAN-10-2720 pmid: 20980433
33	Shachaf CM, Gentles AJ, Elchuri S, Sahoo D, Soen Y, Sharpe O, Perez OD, Chang M, Mitchel D, Robinson WH, Dill D, Nolan GP, Plevritis SK, Felsher DW. Genomic and proteomic analysis reveals a threshold level of MYC required for tumor maintenance. Cancer Res 2008; 68(13): 5132–5142 https://doi.org/10.1158/0008-5472.CAN-07-6192 pmid: 18593912
34	Karlsson A, Giuriato S, Tang F, Fung-Weier J, Levan G, Felsher DW. Genomically complex lymphomas undergo sustained tumor regression upon MYC inactivation unless they acquire novel chromosomal translocations. Blood 2003; 101(7): 2797–2803 https://doi.org/10.1182/blood-2002-10-3091 pmid: 12517816
35	Thomas LR, Wang Q, Grieb BC, Phan J, Foshage AM, Sun Q, Olejniczak ET, Clark T, Dey S, Lorey S, Alicie B, Howard GC, Cawthon B, Ess KC, Eischen CM, Zhao Z, Fesik SW, Tansey WP. Interaction with WDR5 promotes target gene recognition and tumorigenesis by MYC. Mol Cell 2015; 58(3): 440–452 https://doi.org/10.1016/j.molcel.2015.02.028 pmid: 25818646
36	Guccione E, Martinato F, Finocchiaro G, Luzi L, Tizzoni L, Dall’ Olio V, Zardo G, Nervi C, Bernard L, Amati B. Myc-binding-site recognition in the human genome is determined by chromatin context. Nat Cell Biol 2006; 8(7): 764–770 https://doi.org/10.1038/ncb1434 pmid: 16767079
37	Wiese KE, Walz S, von Eyss B, Wolf E, Athineos D, Sansom O, Eilers M. The role of MIZ-1 in MYC-dependent tumorigenesis. Cold Spring Harb Perspect Med 2013; 3(12): a014290 https://doi.org/10.1101/cshperspect.a014290 pmid: 24296348
38	Vo BT, Wolf E, Kawauchi D, Gebhardt A, Rehg JE, Finkelstein D, Walz S, Murphy BL, Youn YH, Han YG, Eilers M, Roussel MF. The interaction of Myc with Miz1 defines medulloblastoma subgroup identity. Cancer Cell 2016; 29(1): 5–16 https://doi.org/10.1016/j.ccell.2015.12.003 pmid: 26766587
39	Hann SR. MYC cofactors: molecular switches controlling diverse biological outcomes. Cold Spring Harb Perspect Med 2014; 4(9): a014399 https://doi.org/10.1101/cshperspect.a014399 pmid: 24939054
40	Lin CY, Lovén J, Rahl PB, Paranal RM, Burge CB, Bradner JE, Lee TI, Young RA. Transcriptional amplification in tumor cells with elevated c-Myc. Cell 2012; 151(1): 56–67 https://doi.org/10.1016/j.cell.2012.08.026 pmid: 23021215
41	Rahl PB, Lin CY, Seila AC, Flynn RA, McCuine S, Burge CB, Sharp PA, Young RA. c-Myc regulates transcriptional pause release. Cell 2010; 141(3):432–445 PMID: 20434984 https://doi.org/10.1016/j.cell.2010.03.030
42	Nie Z, Hu G, Wei G, Cui K, Yamane A, Resch W, Wang R, Green DR, Tessarollo L, Casellas R, Zhao K, Levens D. c-Myc is a universal amplifier of expressed genes in lymphocytes and embryonic stem cells. Cell 2012; 151(1): 68–79 https://doi.org/10.1016/j.cell.2012.08.033 pmid: 23021216
43	Lorenzin F, Benary U, Baluapuri A, Walz S, Jung LA, von Eyss B, Kisker C, Wolf J, Eilers M, Wolf E. Different promoter affinities account for specificity in MYC-dependent gene regulation. eLife 2016; 5: e15161 https://doi.org/10.7554/eLife.15161 pmid: 27460974
44	Whyte WA, Orlando DA, Hnisz D, Abraham BJ, Lin CY, Kagey MH, Rahl PB, Lee TI, Young RA. Master transcription factors and mediator establish super-enhancers at key cell identity genes. Cell 2013; 153(2): 307–319 https://doi.org/10.1016/j.cell.2013.03.035 pmid: 23582322
45	Wolf E, Lin CY, Eilers M, Levens DL. Taming of the beast: shaping Myc-dependent amplification. Trends Cell Biol 2015; 25(4): 241–248 https://doi.org/10.1016/j.tcb.2014.10.006 pmid: 25475704
46	Kress TR, Sabò A, Amati B. MYC: connecting selective transcriptional control to global RNA production. Nat Rev Cancer 2015; 15(10): 593–607 https://doi.org/10.1038/nrc3984 pmid: 26383138
47	Zeid R, Lawlor MA, Poon E, Reyes JM, Fulciniti M, Lopez MA, Scott TG, Nabet B, Erb MA, Winter GE, Jacobson Z, Polaski DR, Karlin KL, Hirsch RA, Munshi NP, Westbrook TF, Chesler L, Lin CY, Bradner JE. Enhancer invasion shapes MYCN-dependent transcriptional amplification in neuroblastoma. Nat Genet 2018; 50(4): 515–523 https://doi.org/10.1038/s41588-018-0044-9 pmid: 29379199
48	Meroni G, Reymond A, Alcalay M, Borsani G, Tanigami A, Tonlorenzi R, Lo Nigro C, Messali S, Zollo M, Ledbetter DH, Brent R, Ballabio A, Carrozzo R. Rox, a novel bHLHZip protein expressed in quiescent cells that heterodimerizes with Max, binds a non-canonical E box and acts as a transcriptional repressor. EMBO J 1997; 16(10): 2892–2906 https://doi.org/10.1093/emboj/16.10.2892 pmid: 9184233
49	Hurlin PJ, Quéva C, Koskinen PJ, Steingrímsson E, Ayer DE, Copeland NG, Jenkins NA, Eisenman RN. Mad3 and Mad4: novel Max-interacting transcriptional repressors that suppress c-myc dependent transformation and are expressed during neural and epidermal differentiation. EMBO J 1995; 14(22): 5646–5659 pmid: 8521822
50	Zervos AS, Gyuris J, Brent R. Mxi1, a protein that specifically interacts with Max to bind Myc-Max recognition sites. Cell 1993; 72(2): 223–232 https://doi.org/10.1016/0092-8674(93)90662-A pmid: 8425219
51	Ayer DE, Kretzner L, Eisenman RN. Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity. Cell 1993; 72(2): 211–222 https://doi.org/10.1016/0092-8674(93)90661-9 pmid: 8425218
52	Hurlin PJ, Steingrìmsson E, Copeland NG, Jenkins NA, Eisenman RN. Mga, a dual-specificity transcription factor that interacts with Max and contains a T-domain DNA-binding motif. EMBO J 1999; 18(24): 7019–7028 https://doi.org/10.1093/emboj/18.24.7019 pmid: 10601024
53	Papaioannou VE, Silver LM. The T-box gene family. BioEssays 1998; 20(1): 9–19 https://doi.org/10.1002/(SICI)1521-1878(199801)20:1<9::AID-BIES4>3.0.CO;2-Q pmid: 9504043
54	Kispert A, Koschorz B, Herrmann BG. The T protein encoded by Brachyury is a tissue-specific transcription factor. EMBO J 1995; 14(19): 4763–4772 pmid: 7588606
55	Kispert A, Herrmann BG. The Brachyury gene encodes a novel DNA binding protein. EMBO J 1993; 12(8): 3211–3220 pmid: 8344258
56	Ferré-D’Amaré AR, Prendergast GC, Ziff EB, Burley SK. Recognition by Max of its cognate DNA through a dimeric b/HLH/Z domain. Nature 1993; 363(6424): 38–45 https://doi.org/10.1038/363038a0 pmid: 8479534
57	Brubaker K, Cowley SM, Huang K, Loo L, Yochum GS, Ayer DE, Eisenman RN, Radhakrishnan I. Solution structure of the interacting domains of the Mad-Sin3 complex: implications for recruitment of a chromatin-modifying complex. Cell 2000; 103(4): 655–665 https://doi.org/10.1016/S0092-8674(00)00168-9 pmid: 11106735
58	Ayer DE, Lawrence QA, Eisenman RN. Mad-Max transcriptional repression is mediated by ternary complex formation with mammalian homologs of yeast repressor Sin3. Cell 1995; 80(5): 767–776 https://doi.org/10.1016/0092-8674(95)90355-0 pmid: 7889570
59	Zhang Y, Iratni R, Erdjument-Bromage H, Tempst P, Reinberg D. Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex. Cell 1997; 89(3): 357–364 https://doi.org/10.1016/S0092-8674(00)80216-0 pmid: 9150135
60	Laherty CD, Yang WM, Sun JM, Davie JR, Seto E, Eisenman RN. Histone deacetylases associated with the mSin3 corepressor mediate mad transcriptional repression. Cell 1997; 89(3): 349–356 https://doi.org/10.1016/S0092-8674(00)80215-9 pmid: 9150134
61	Hassig CA, Fleischer TC, Billin AN, Schreiber SL, Ayer DE. Histone deacetylase activity is required for full transcriptional repression by mSin3A. Cell 1997; 89(3): 341–347 https://doi.org/10.1016/S0092-8674(00)80214-7 pmid: 9150133
62	Gao Z, Zhang J, Bonasio R, Strino F, Sawai A, Parisi F, Kluger Y, Reinberg D. PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes. Mol Cell 2012; 45(3): 344–356 https://doi.org/10.1016/j.molcel.2012.01.002 pmid: 22325352
63	Ogawa H, Ishiguro K, Gaubatz S, Livingston DM, Nakatani Y. A complex with chromatin modifiers that occupies E2F- and Myc-responsive genes in G0 cells. Science 2002; 296(5570): 1132–1136 https://doi.org/10.1126/science.1069861 pmid: 12004135
64	Endoh M, Endo TA, Shinga J, Hayashi K, Farcas A, Ma KW, Ito S, Sharif J, Endoh T, Onaga N, Nakayama M, Ishikura T, Masui O, Kessler BM, Suda T, Ohara O, Okuda A, Klose R, Koseki H. PCGF6–PRC1 suppresses premature differentiation of mouse embryonic stem cells by regulating germ cell-related genes. eLife 2017; 6:e21064 https://doi.org/10.7554/eLife.21064
65	Suzuki A, Hirasaki M, Hishida T, Wu J, Okamura D, Ueda A, Nishimoto M, Nakachi Y, Mizuno Y, Okazaki Y, Matsui Y, Izpisua Belmonte JC, Okuda A. Loss of MAX results in meiotic entry in mouse embryonic and germline stem cells. Nat Commun 2016; 7: 11056 https://doi.org/10.1038/ncomms11056 pmid: 27025988
66	McFerrin LG, Atchley WR. Evolution of the Max and Mlx networks in animals. Genome Biol Evol 2011; 3:915–937 PMID: 21859806 https://doi.org/10.1093/gbe/evr082
67	Washkowitz AJ, Schall C, Zhang K, Wurst W, Floss T, Mager J, Papaioannou VE. Mga is essential for the survival of pluripotent cells during peri-implantation development. Development 2015; 142(1): 31–40 https://doi.org/10.1242/dev.111104 pmid: 25516968
68	Sun Y, Tseng WC, Fan X, Ball R, Dougan ST. Extraembryonic signals under the control of MGA, Max, and Smad4 are required for dorsoventral patterning. Dev Cell 2014; 28(3): 322–334 https://doi.org/10.1016/j.devcel.2014.01.003 pmid: 24525188
69	Hu G, Kim J, Xu Q, Leng Y, Orkin SH, Elledge SJ. A genome-wide RNAi screen identifies a new transcriptional module required for self-renewal. Genes Dev 2009; 23(7): 837–848 https://doi.org/10.1101/gad.1769609 pmid: 19339689
70	Sun QY, Ding LW, Tan KT, Chien W, Mayakonda A, Lin DC, Loh XY, Xiao JF, Meggendorfer M, Alpermann T, Garg M, Lim SL, Madan V, Hattori N, Nagata Y, Miyano S, Yeoh AE, Hou HA, Jiang YY, Takao S, Liu LZ, Tan SZ, Lill M, Hayashi M, Kinoshita A, Kantarjian HM, Kornblau SM, Ogawa S, Haferlach T, Yang H, Koeffler HP. Ordering of mutations in acute myeloid leukemia with partial tandem duplication of MLL (MLL-PTD). Leukemia 2017; 31(1): 1–10 https://doi.org/10.1038/leu.2016.160 pmid: 27389053
71	Romero OA, Torres-Diz M, Pros E, Savola S, Gomez A, Moran S, Saez C, Iwakawa R, Villanueva A, Montuenga LM, Kohno T, Yokota J, Sanchez-Cespedes M. MAX inactivation in small cell lung cancer disrupts MYC-SWI/SNF programs and is synthetic lethal with BRG1. Cancer Discov 2014; 4(3): 292–303 https://doi.org/10.1158/2159-8290.CD-13-0799 pmid: 24362264
72	De Paoli L, Cerri M, Monti S, Rasi S, Spina V, Bruscaggin A, Greco M, Ciardullo C, Famà R, Cresta S, Maffei R, Ladetto M, Martini M, Laurenti L, Forconi F, Marasca R, Larocca LM, Bertoni F, Gaidano G, Rossi D. MGA, a suppressor of MYC, is recurrently inactivated in high risk chronic lymphocytic leukemia. Leuk Lymphoma 2013; 54(5): 1087–1090 https://doi.org/10.3109/10428194.2012.723706 pmid: 23039309
73	Chigrinova E, Rinaldi A, Kwee I, Rossi D, Rancoita PM, Strefford JC, Oscier D, Stamatopoulos K, Papadaki T, Berger F, Young KH, Murray F, Rosenquist R, Greiner TC, Chan WC, Orlandi EM, Lucioni M, Marasca R, Inghirami G, Ladetto M, Forconi F, Cogliatti S, Votavova H, Swerdlow SH, Stilgenbauer S, Piris MA, Matolcsy A, Spagnolo D, Nikitin E, Zamò A, Gattei V, Bhagat G, Ott G, Zucca E, Gaidano G, Bertoni F. Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter syndrome. Blood 2013; 122(15): 2673–2682 https://doi.org/10.1182/blood-2013-03-489518 pmid: 24004666
74	Edelmann J, Holzmann K, Miller F, Winkler D, Bühler A, Zenz T, Bullinger L, Kühn MW, Gerhardinger A, Bloehdorn J, Radtke I, Su X, Ma J, Pounds S, Hallek M, Lichter P, Korbel J, Busch R, Mertens D, Downing JR, Stilgenbauer S, Döhner H. High-resolution genomic profiling of chronic lymphocytic leukemia reveals new recurrent genomic alterations. Blood 2012; 120(24): 4783–4794 https://doi.org/10.1182/blood-2012-04-423517 pmid: 23047824
75	McFerrin LG, Atchley WR. A novel N-terminal domain may dictate the glucose response of Mondo proteins. PLoS One 2012; 7(4): e34803 https://doi.org/10.1371/journal.pone.0034803 pmid: 22506051
76	Arden C, Tudhope SJ, Petrie JL, Al-Oanzi ZH, Cullen KS, Lange AJ, Towle HC, Agius L. Fructose 2,6-bisphosphate is essential for glucose-regulated gene transcription of glucose-6-phosphatase and other ChREBP target genes in hepatocytes. Biochem J 2012; 443(1): 111–123 https://doi.org/10.1042/BJ20111280 pmid: 22214556
77	Petrie JL, Al-Oanzi ZH, Arden C, Tudhope SJ, Mann J, Kieswich J, Yaqoob MM, Towle HC, Agius L. Glucose induces protein targeting to glycogen in hepatocytes by fructose 2,6-bisphosphate-mediated recruitment of MondoA to the promoter. Mol Cell Biol 2013; 33(4): 725–738 https://doi.org/10.1128/MCB.01576-12 pmid: 23207906
78	Sans CL, Satterwhite DJ, Stoltzman CA, Breen KT, Ayer DE. MondoA-Mlx heterodimers are candidate sensors of cellular energy status: mitochondrial localization and direct regulation of glycolysis. Mol Cell Biol 2006; 26(13): 4863–4871 https://doi.org/10.1128/MCB.00657-05 pmid: 16782875
79	Peterson CW, Stoltzman CA, Sighinolfi MP, Han KS, Ayer DE. Glucose controls nuclear accumulation, promoter binding, and transcriptional activity of the MondoA-Mlx heterodimer. Mol Cell Biol 2010; 30(12):2887–2895 PMID: 20385767 https://doi.org/10.1128/MCB.01613-09
80	Stoltzman CA, Peterson CW, Breen KT, Muoio DM, Billin AN, Ayer DE. Glucose sensing by MondoA:Mlx complexes: a role for hexokinases and direct regulation of thioredoxin-interacting protein expression. Proc Natl Acad Sci U S A 2008;105(19):6912–6917 PMID: 18458340 https://doi.org/10.1073/pnas.0712199105
81	Mattila J, Havula E, Suominen E, Teesalu M, Surakka I, Hynynen R, Kilpinen H, Väänänen J, Hovatta I, Käkelä R, Ripatti S, Sandmann T, Hietakangas V. Mondo-Mlx mediates organismal sugar sensing through the Gli-similar transcription factor sugarbabe. Cell Reports 2015; 13(2): 350–364 https://doi.org/10.1016/j.celrep.2015.08.081 pmid: 26440885
82	Havula E, Teesalu M, Hyötyläinen T, Seppälä H, Hasygar K, Auvinen P, Orešič M, Sandmann T, Hietakangas V. Mondo/ChREBP-Mlx-regulated transcriptional network is essential for dietary sugar tolerance in Drosophila. PLoS Genet 2013; 9(4): e1003438 https://doi.org/10.1371/journal.pgen.1003438 pmid: 23593032
83	Iizuka K. The transcription factor carbohydrate-response element-binding protein (ChREBP): a possible link between metabolic disease and cancer. Biochim Biophys Acta 2017; 1863(2): 474–485 https://doi.org/10.1016/j.bbadis.2016.11.029 pmid: 27919710
84	Dang CV, Eisenman RN. Myc and the Pathway to Cancer. Cold Spring Harbor, N.Y.: Cold Spring Harbor Press, 2014
85	Comino-Mendez I, Gracia-Aznarez FJ, Schiavi F, Landa I, Leandro-Garcia LJ, Leton R, Honrado E, Ramos-Medina R, Caronia D, Pita G, Gomez-Grana A, de Cubas AA, Inglada-Perez L, Maliszewska A, Taschin E, Bobisse S, Pica G, Loli P, Hernandez-Lavado R, Diaz JA, Gomez-Morales M, Gonzalez-Neira A, Roncador G, Rodriguez-Antona C, Benitez J, Mannelli M, Opocher G, Robledo M, Cascon A. Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma. Nat Genet 2011;43(7):663–667 PMID: 21685915 https://doi.org/10.1038/ng.861
86	Toyo-oka K, Bowen TJ, Hirotsune S, Li Z, Jain S, Ota S, Escoubet-Lozach L, Garcia-Bassets I, Lozach J, Rosenfeld MG, Glass CK, Eisenman R, Ren B, Hurlin P, Wynshaw-Boris A. Mnt-deficient mammary glands exhibit impaired involution and tumors with characteristics of myc overexpression. Cancer Res 2006; 66(11): 5565–5573 https://doi.org/10.1158/0008-5472.CAN-05-2683 pmid: 16740691
87	Dezfouli S, Bakke A, Huang J, Wynshaw-Boris A, Hurlin PJ. Inflammatory disease and lymphomagenesis caused by deletion of the Myc antagonist Mnt in T cells. Mol Cell Biol 2006; 26(6): 2080–2092 https://doi.org/10.1128/MCB.26.6.2080-2092.2006 pmid: 16507988
88	Lahoz EG, Xu L, Schreiber-Agus N, DePinho RA. Suppression of Myc, but not E1a, transformation activity by Max-associated proteins, Mad and Mxi1. Proc Natl Acad Sci USA 1994; 91(12): 5503–5507 https://doi.org/10.1073/pnas.91.12.5503 pmid: 8202517
89	Iritani BM, Delrow J, Grandori C, Gomez I, Klacking M, Carlos LS, Eisenman RN. Modulation of T-lymphocyte development, growth and cell size by the Myc antagonist and transcriptional repressor Mad1. Embo J 2002; 21(18):4820–4830 pmid: 12234922
90	Roussel MF, Ashmun RA, Sherr CJ, Eisenman RN, Ayer DE. Inhibition of cell proliferation by the Mad1 transcriptional repressor. Mol Cell Biol 1996; 16(6): 2796–2801 https://doi.org/10.1128/MCB.16.6.2796 pmid: 8649388
91	Marcotte R, Qian JF, Chen J, Wang E. hMad4, c-Myc endogenous inhibitor, induces a replicative senescence-like state when overexpressed in human fibroblasts. J Cell Biochem 2003; 89(3): 576–588 https://doi.org/10.1002/jcb.10517 pmid: 12761891
92	Walker W, Zhou ZQ, Ota S, Wynshaw-Boris A, Hurlin PJ. Mnt-Max to Myc-Max complex switching regulates cell cycle entry. J Cell Biol 2005; 169(3): 405–413 https://doi.org/10.1083/jcb.200411013 pmid: 15866886
93	Link JM, Ota S, Zhou ZQ, Daniel CJ, Sears RC, Hurlin PJ. A critical role for Mnt in Myc-driven T-cell proliferation and oncogenesis. Proc Natl Acad Sci USA 2012; 109(48): 19685–19690 https://doi.org/10.1073/pnas.1206406109 pmid: 23150551
94	Yang G, Hurlin PJ. MNT and emerging concepts of MNT-MYC antagonism. Genes (Basel) 2017; 8(2): E83 https://doi.org/10.3390/genes8020083 pmid: 28230739
95	Yun JS, Rust JM, Ishimaru T, Diaz E. A novel role of the Mad family member Mad3 in cerebellar granule neuron precursor proliferation. Mol Cell Biol 2007; 27(23):8178–8189 https://doi.org/10.1128/MCB.00656-06 pmid: 17893326
96	Quéva C, McArthur GA, Iritani BM, Eisenman RN. Targeted deletion of the S-phase-specific Myc antagonist Mad3 sensitizes neuronal and lymphoid cells to radiation-induced apoptosis. Mol Cell Biol 2001; 21(3): 703–712 https://doi.org/10.1128/MCB.21.3.703-712.2001 pmid: 11154258
97	Hooker CW, Hurlin PJ. Of Myc and Mnt. J Cell Sci 2006; 119(Pt 2): 208–216 https://doi.org/10.1242/jcs.02815 pmid: 16410546
98	Bouchard C, Dittrich O, Kiermaier A, Dohmann K, Menkel A, Eilers M, Lüscher B. Regulation of cyclin D2 gene expression by the Myc/Max/Mad network: Myc-dependent TRRAP recruitment and histone acetylation at the cyclin D2 promoter. Genes Dev 2001; 15(16): 2042–2047 https://doi.org/10.1101/gad.907901 pmid: 11511535
99	Pierce SB, Yost C, Anderson SA, Flynn EM, Delrow J, Eisenman RN. Drosophila growth and development in the absence of dMyc and dMnt. Dev Biol 2008; 315(2): 303–316 https://doi.org/10.1016/j.ydbio.2007.12.026 pmid: 18241851
100	Beall EL, Bell M, Georlette D, Botchan MR. Dm-myb mutant lethality in Drosophila is dependent upon mip130: positive and negative regulation of DNA replication. Genes Dev 2004; 18(14): 1667–1680 https://doi.org/10.1101/gad.1206604 pmid: 15256498
101	Frolov MV, Huen DS, Stevaux O, Dimova D, Balczarek-Strang K, Elsdon M, Dyson NJ. Functional antagonism between E2F family members. Genes Dev 2001; 15(16): 2146–2160 https://doi.org/10.1101/gad.903901 pmid: 11511545
102	Welcker M, Orian A, Jin J, Grim JE, Harper JW, Eisenman RN, Clurman BE. The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation. Proc Natl Acad Sci USA 2004; 101(24): 9085–9090 https://doi.org/10.1073/pnas.0402770101 pmid: 15150404
103	Farrell A, Sears RC. MYC Degradation. Cold Spring Harb Prespect Med 2014; 4:a014365 https://doi.org/10.1101/cshperspect.a014365
104	Zhu J, Blenis J, Yuan J. Activation of PI3K/Akt and MAPK pathways regulates Myc-mediated transcription by phosphorylating and promoting the degradation of Mad1. Proc Natl Acad Sci USA 2008; 105(18): 6584–6589 https://doi.org/10.1073/pnas.0802785105 pmid: 18451027
105	Steiger D, Furrer M, Schwinkendorf D, Gallant P.Max-independent functions of Myc in Drosophila melanogaster. Nat Genet 2008; 40(9):1084–1091 https://doi.org/10.1038/ng.178 pmid: 19165923
106	Dejure FR, Eilers M. MYC and tumor metabolism: chicken and egg. EMBO J 2017; 36(23): 3409–3420 https://doi.org/10.15252/embj.201796438 pmid: 29127156
107	Carroll PA, Diolaiti D, McFerrin L, Gu H, Djukovic D, Du J, Cheng PF, Anderson S, Ulrich M, Hurley JB, Raftery D, Ayer DE, Eisenman RN. Deregulated Myc requires MondoA/Mlx for metabolic reprogramming and tumorigenesis. Cancer Cell 2015; 27(2): 271–285 https://doi.org/10.1016/j.ccell.2014.11.024 pmid: 25640402
108	Chan LN, Chen Z, Braas D, Lee JW, Xiao G, Geng H, Cosgun KN, Hurtz C, Shojaee S, Cazzaniga V, Schjerven H, Ernst T, Hochhaus A, Kornblau SM, Konopleva M, Pufall MA, Cazzaniga G, Liu GJ, Milne TA, Koeffler HP, Ross TS, Sánchez-García I, Borkhardt A, Yamamoto KR, Dickins RA, Graeber TG, Müschen M. Metabolic gatekeeper function of B-lymphoid transcription factors. Nature 2017; 542(7642): 479–483 https://doi.org/10.1038/nature21076 pmid: 28192788
109	Nakamura S, Karalay Ö, Jäger PS, Horikawa M, Klein C, Nakamura K, Latza C, Templer SE, Dieterich C, Antebi A. Mondo complexes regulate TFEB via TOR inhibition to promote longevity in response to gonadal signals. Nat Commun 2016; 7: 10944 https://doi.org/10.1038/ncomms10944 pmid: 27001890
110	Taniguchi M, Sasaki-Osugi K, Oku M, Sawaguchi S, Tanakura S, Kawai Y, Wakabayashi S, Yoshida H. MLX Is a transcriptional repressor of the mammalian Golgi stress response. Cell Struct Funct 2016; 41(2): 93–104 https://doi.org/10.1247/csf.16005 pmid: 27251850
111	Hunt LC, Xu B, Finkelstein D, Fan Y, Carroll PA, Cheng PF, Eisenman RN, Demontis F. The glucose-sensing transcription factor MLX promotes myogenesis via myokine signaling. Genes Dev 2015; 29(23): 2475–2489 https://doi.org/10.1101/gad.267419.115 pmid: 26584623
112	Kanatsu-Shinohara M, Tanaka T, Ogonuki N, Ogura A, Morimoto H, Cheng PF, Eisenman RN, Trumpp A, Shinohara T. Myc/Mycn-mediated glycolysis enhances mouse spermatogonial stem cell self-renewal. Genes Dev 2016; 30(23): 2637–2648 https://doi.org/10.1101/gad.287045.116 pmid: 28007786
113	Shen L, O’Shea JM, Kaadige MR, Cunha S, Wilde BR, Cohen AL, Welm AL, Ayer DE. Metabolic reprogramming in triple-negative breast cancer through Myc suppression of TXNIP. Proc Natl Acad Sci USA 2015; 112(17): 5425–5430 https://doi.org/10.1073/pnas.1501555112 pmid: 25870263
114	Parmenter TJ, Kleinschmidt M, Kinross KM, Bond ST, Li J, Kaadige MR, Rao A, Sheppard KE, Hugo W, Pupo GM, Pearson RB, McGee SL, Long GV, Scolyer RA, Rizos H, Lo RS, Cullinane C, Ayer DE, Ribas A, Johnstone RW, Hicks RJ, McArthur GA. Response of BRAF-mutant melanoma to BRAF inhibition is mediated by a network of transcriptional regulators of glycolysis. Cancer Discov 2014; 4(4): 423–433 https://doi.org/10.1158/2159-8290.CD-13-0440 pmid: 24469106
115	Wilde BR, Ayer DE. Interactions between Myc and MondoA transcription factors in metabolism and tumourigenesis. Br J Cancer 2015; 113(11): 1529–1533 https://doi.org/10.1038/bjc.2015.360 pmid: 26469830
116	Jolma A, Yin Y, Nitta KR, Dave K, Popov A, Taipale M, Enge M, Kivioja T, Morgunova E, Taipale J. DNA-dependent formation of transcription factor pairs alters their binding specificity. Nature 2015; 527(7578): 384–388 https://doi.org/10.1038/nature15518 pmid: 26550823
117	Morgunova E, Taipale J. Structural perspective of cooperative transcription factor binding. Curr Opin Struct Biol 2017; 47: 1–8 https://doi.org/10.1016/j.sbi.2017.03.006 pmid: 28349863
118	Yan J, Enge M, Whitington T, Dave K, Liu J, Sur I, Schmierer B, Jolma A, Kivioja T, Taipale M, Taipale J. Transcription factor binding in human cells occurs in dense clusters formed around cohesin anchor sites. Cell 2013; 154(4): 801–813 https://doi.org/10.1016/j.cell.2013.07.034 pmid: 23953112
119	Ma L, Sham YY, Walters KJ, Towle HC. A critical role for the loop region of the basic helix-loop-helix/leucine zipper protein Mlx in DNA binding and glucose-regulated transcription. Nucleic Acids Res 2007; 35(1): 35–44 https://doi.org/10.1093/nar/gkl987 pmid: 17148476
120	Skinner MK, Rawls A, Wilson-Rawls J, Roalson EH. Basic helix-loop-helix transcription factor gene family phylogenetics and nomenclature. Differentiation 2010; 80(1): 1–8 https://doi.org/10.1016/j.diff.2010.02.003 pmid: 20219281
121	Altman BJ, Hsieh AL, Sengupta A, Krishnanaiah SY, Stine ZE, Walton ZE, Gouw AM, Venkataraman A, Li B, Goraksha-Hicks P, Diskin SJ, Bellovin DI, Simon MC, Rathmell JC, Lazar MA, Maris JM, Felsher DW, Hogenesch JB, Weljie AM, Dang CV. MYC disrupts the circadian clock and metabolism in cancer cells. Cell Metab 2015; 22(6): 1009–1019 https://doi.org/10.1016/j.cmet.2015.09.003 pmid: 26387865
122	Qing G, Skuli N, Mayes PA, Pawel B, Martinez D, Maris JM, Simon MC. Combinatorial regulation of neuroblastoma tumor progression by N-Myc and hypoxia inducible factor HIF-1α. Cancer Res 2010; 70(24):10351–10361 https://doi.org/10.1158/0008-5472.CAN-10-0740 pmid: 20961996

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