Aldolase B attenuates clear cell renal cell carcinoma progression by inhibiting CtBP2

doi:10.1007/s11684-022-0947-9

Front. Med.

2023, Vol. 17

Issue (3) : 503-517 https://doi.org/10.1007/s11684-022-0947-9

RESEARCH ARTICLE

Aldolase B attenuates clear cell renal cell carcinoma progression by inhibiting CtBP2

Mingyue Tan^1,², Qi Pan¹, Qi Wu^1,³, Jianfa Li¹, Jun Wang^1,^2,³(

)

¹. Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
². Urology Center, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
³. Department of Urology, The Sixth Affiliated Hospital of Wenzhou Medical University (The People’s Hospital of Lishui), Lishui 323000, China

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Abstract

Aldolase B (ALDOB), a glycolytic enzyme, is uniformly depleted in clear cell renal cell carcinoma (ccRCC) tissues. We previously showed that ALDOB inhibited proliferation through a mechanism independent of its enzymatic activity in ccRCC, but the mechanism was not unequivocally identified. We showed that the corepressor C-terminal-binding protein 2 (CtBP2) is a novel ALDOB-interacting protein in ccRCC. The CtBP2-to-ALDOB expression ratio in clinical samples was correlated with the expression of CtBP2 target genes and was associated with shorter survival. ALDOB inhibited CtBP2-mediated repression of multiple cell cycle inhibitor, proapoptotic, and epithelial marker genes. Furthermore, ALDOB overexpression decreased the proliferation and migration of ccRCC cells in an ALDOB-CtBP2 interaction-dependent manner. Mechanistically, our findings showed that ALDOB recruited acireductone dioxygenase 1, which catalyzes the synthesis of an endogenous inhibitor of CtBP2, 4-methylthio 2-oxobutyric acid. ALDOB functions as a scaffold to bring acireductone dioxygenase and CtBP2 in close proximity to potentiate acireductone dioxygenase-mediated inhibition of CtBP2, and this scaffolding effect was independent of ALDOB enzymatic activity. Moreover, increased ALDOB expression inhibited tumor growth in a xenograft model and decreased lung metastasis in vivo. Our findings reveal that ALDOB is a negative regulator of CtBP2 and inhibits tumor growth and metastasis in ccRCC.

Keywords ALDOB kidney cancer cell proliferation

Corresponding Author(s): Jun Wang

Just Accepted Date: 25 November 2022 Online First Date: 15 February 2023 Issue Date: 28 July 2023

Cite this article:

Mingyue Tan,Qi Pan,Qi Wu, et al. Aldolase B attenuates clear cell renal cell carcinoma progression by inhibiting CtBP2[J]. Front. Med., 2023, 17(3): 503-517.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-022-0947-9
https://academic.hep.com.cn/fmd/EN/Y2023/V17/I3/503

Fig.1

Fig.2 The CtBP2-to-ALDOB expression ratio correlates with CtBP2 target gene expression and is associated with shorter survival. (A) Boxplot of the relative CTBP2-to-ALDOB expression ratio in normal kidneys and ccRCC tissues (N = 30). (B, C) Boxplot of the relative CTBP2 (B) and ALDOB (C) expression levels in normal kidneys and ccRCC tissues (N = 30). (D–G) A scatter plot was used to visualize the relationship between the CtBP2/ALDOB expression ratio and the expression of target genes (CDH1 (D), CDKN2C (E), BIK (F), and BAX (G)) in ccRCC tissues (N = 30). (H,I) A scatter plot was used to visualize the relationship between the CtBP2/ALDOB expression ratio and the expression of target genes (CDH1 (H) and CDKN1C (I)) in the TCGA-KIRC data set. (J,K) A scatter plot was used to visualize the relationship between the CtBP2/ALDOB expression ratio and the protein levels of p21 (J) and Bax (K) in the TCGA-KIRC data set. (L) The consensus map of RNA sequencing (RNA-seq) data from ccRCC samples calculated with the NMF algorithm (cluster number = 3). (M) Violin plots of the CtBP2/ALDOB ratio within Clusters 1, 2, and 3. (N) Curves showing the overall survival of 516 patients with ccRCC from the TCGA-KIRC data set. These patients were divided into Clusters 1, 2, and 3 according to the NMF algorithm. (O,P) Curves showing the overall survival (O) and disease-free survival (P) of 516 patients with ccRCC from the TCGA-KIRC data set. These patients were divided into low and high groups according to the median CTBP2/ALDOB ratio. HRs and P values for survival curves were calculated using the log-rank test.

Fig.3 ALDOB releases CtBP2-mediated repression of target gene expression. (A,B) Real-time PCR analysis of the expression of CtBP2 target genes in Caki-1 (A) and 769-P (B) cells stably transfected with Ctrl or ALDOB. (C) ALDOB enzyme activity in Caki-1 and OSRC-2 cells transiently transfected with siCtrl, siCtBP2#1, or siCtBP2#2. (D) Caki-1 cells infected with different doses of a lentivirus expressing ALDOB were subjected to WB with the indicated antibody 7 days after infection. (E) Caki-1 cells stably expressing Ctrl and ALDOB were subjected to nuclear and cytosolic fractionation and analysis. Tubulin and Lamin B served as the loading controls for the cytosolic and nuclear fractions, respectively. (F,G) The 786-O cells stably expressing Ctrl and ALDOB were transiently transfected with a CDH1 promoter luciferase reporter and siCtrl or siCtBP2#1 and subjected to WB (F) and a luciferase assay (G) 72 h after transfection. (H) ALDOB overexpression resulted in reduced binding of CtBP2 to the promoter regions of the CDH1, PTEN, CDKN1A, and BAX genes. ChIP assays of the E-cadherin, PTEN, p21, and Bax promoters were performed using chromatin obtained from Ctrl- or ALDOB-expressing Caki-1 cells. After immunoprecipitation with anti-CtBP2 or control IgG antibodies, immunoprecipitated DNA was quantified using qPCR with primers specific for the indicated promoter. (I) The 293T cells were transfected with HA-CtBP2, Flag-ALDOB^WT, Flag-ALDOB^K147A, Flag-ALDOB^K230A, Flag-ALDOB^R304A or Flag-ALDOB^A318E. Twenty-four hours after transfection, the cells were subjected to IP using an anti-HA antibody. (J) ALDOB enzyme activity in 293T cells transiently transfected with ALDOB^WT or ALDOB^A318E. (K) Real-time PCR analysis of the expression of CtBP2 target genes in Caki-1 cells stably transfected with Ctrl, ALDOB^WT, and ALDOB^A318E. (L) The 786-O cells stably expressing Ctrl, ALDOB^WT and ALDOB^A318E were transiently transfected with a CDH1 promoter luciferase reporter and subjected to a luciferase assay 48 h after transfection. * indicates P < 0.05.

Fig.4 ALDOB inhibits ccRCC cell proliferation and migration partially by interacting with CtBP2. (A) Caki-1 cells stably expressing the vector (Ctrl), ALDOB^WT or ALDOB^A318E were subjected to WB analysis using an anti-ALDOB antibody. (B) Growth curves of Caki-1 cells stably expressing Ctrl, ALDOB^WT, or ALDOB^A318E. (C) Growth curves of 786-O cells stably expressing Ctrl, ALDOB^WT, or ALDOB^A318E. (D,E) Cell cycle analysis of Caki-1 (D) and 786-O (E) cells stably expressing an empty vector (Ctrl), ALDOB^WT, or ALDOB^A318E based on a BrdU incorporation assay. (F,G) Percentage of apoptotic Caki-1 (F) and OSRC-2 (G) cells stably expressing an empty vector (Ctrl), ALDOB^WT, or ALDOB^A318E 2 h after treatment with 0.1 nM staurosporine, according to annexin V and propidium iodide (PI) staining. (H, I) Wound healing assay of Caki-1 (H) and 786-O (I) cells stably expressing Ctrl, ALDOB^WT or ALDOB^A318E. Scale bar = 200 μm. (J,K) Transwell assays of Caki-1 (J) and 786-O (K) cells stably expressing Ctrl, ALDOB^WT, or ALDOB^A318E. Images were captured at 200× magnification.

Fig.5

Fig.6 Schematic diagram. ALDOB acts as a scaffold protein that brings ADI1 and CtBP2 in close proximity. ALDOB potentiates ADI1-mediated inhibition of CtBP2. This biological process impairs the transcriptional repression mediated by CtBP2 and is involved in regulating cell proliferation and migration in kidney cancer.

1	RL Siegel, KD Miller, A Jemal. Cancer statistics, 2020. CA Cancer J Clin 2020; 70(1): 7–30 https://doi.org/10.3322/caac.21590 pmid: 31912902
2	TJ Mitchell, S Turajlic, A Rowan, D Nicol, JHR Farmery, T O’Brien, I Martincorena, P Tarpey, N Angelopoulos, LR Yates, AP Butler, K Raine, GD Stewart, B Challacombe, A Fernando, JI Lopez, S Hazell, A Chandra, S Chowdhury, S Rudman, A Soultati, G Stamp, N Fotiadis, L Pickering, L Au, L Spain, J Lynch, M Stares, J Teague, F Maura, DC Wedge, S Horswell, T Chambers, K Litchfield, H Xu, A Stewart, R Elaidi, S Oudard, N McGranahan, I Csabai, M Gore, PA Futreal, J Larkin, AG Lynch, Z Szallasi, C Swanton, PJ Campbell, TRR Consortium. Timing the landmark events in the evolution of clear cell renal cell cancer: TRACERx renal. Cell 2018; 173(3): 611–623.e17 https://doi.org/10.1016/j.cell.2018.02.020 pmid: 29656891
3	J Schödel, S Grampp, ER Maher, H Moch, PJ Ratcliffe, P Russo, DR Mole. Hypoxia, hypoxia-inducible transcription factors, and renal cancer. Eur Urol 2016; 69(4): 646–657 https://doi.org/10.1016/j.eururo.2015.08.007 pmid: 26298207
4	L Lv, Q Lei. Proteins moonlighting in tumor metabolism and epigenetics. Front Med 2021; 15(3): 383–403 https://doi.org/10.1007/s11684-020-0818-1 pmid: 33387254
5	CS Zhang, SA Hawley, Y Zong, M Li, Z Wang, A Gray, T Ma, J Cui, JW Feng, M Zhu, YQ Wu, TY Li, Z Ye, SY Lin, H Yin, HL Piao, DG Hardie, SC Lin. Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK. Nature 2017; 548(7665): 112–116 https://doi.org/10.1038/nature23275 pmid: 28723898
6	M Li, X He, W Guo, H Yu, S Zhang, N Wang, G Liu, R Sa, X Shen, Y Jiang, Y Tang, Y Zhuo, C Yin, Q Tu, N Li, X Nie, Y Li, Z Hu, H Zhu, J Ding, Z Li, T Liu, F Zhang, H Zhou, S Li, J Yue, Z Yan, S Cheng, Y Tao, H Yin. Aldolase B suppresses hepatocellular carcinogenesis by inhibiting G6PD and pentose phosphate pathways. Nat Can 2020; 1(7): 735–747 https://doi.org/10.1038/s43018-020-0086-7 pmid: 35122041
7	J Huang, W Kong, J Zhang, Y Chen, W Xue, D Liu, Y Huang. c-Myc modulates glucose metabolism via regulation of miR-184/PKM2 pathway in clear-cell renal cell carcinoma. Int J Oncol 2016; 49(4): 1569–1575 https://doi.org/10.3892/ijo.2016.3622 pmid: 27431728
8	KD Courtney, D Bezwada, T Mashimo, K Pichumani, V Vemireddy, AM Funk, J Wimberly, SS McNeil, P Kapur, Y Lotan, V Margulis, JA Cadeddu, I Pedrosa, RJ DeBerardinis, CR Malloy, RM Bachoo, EA Maher. Isotope tracing of human clear cell renal cell carcinomas demonstrates suppressed glucose oxidation in vivo. Cell Metab 2018; 28(5): 793–800.e2 https://doi.org/10.1016/j.cmet.2018.07.020 pmid: 30146487
9	HI Wettersten, OA Aboud, PN Jr Lara, RH Weiss. Metabolic reprogramming in clear cell renal cell carcinoma. Nat Rev Nephrol 2017; 13(7): 410–419 https://doi.org/10.1038/nrneph.2017.59 pmid: 28480903
10	J Wang, Q Wu, J Qiu. Accumulation of fructose 1,6-bisphosphate protects clear cell renal cell carcinoma from oxidative stress. Lab Invest 2019; 99(6): 898–908 https://doi.org/10.1038/s41374-019-0203-3 pmid: 30760861
11	Y Lu, Y Li, Q Liu, N Tian, P Du, F Zhu, Y Han, X Liu, X Liu, X Peng, X Wang, Y Wu, L Tong, Y Li, Y Zhu, L Wu, P Zhang, Y Xu, H Chen, B Li, X Tong. MondoA-thioredoxin-interacting protein axis maintains regulatory T-cell identity and function in colorectal cancer microenvironment. Gastroenterology 2021; 161(2): 575–591.e16 https://doi.org/10.1053/j.gastro.2021.04.041 pmid: 33901495
12	P Martinelli, Santa Pau E Carrillo-de, T Cox, B Jr Sainz, N Dusetti, W Greenhalf, L Rinaldi, E Costello, P Ghaneh, N Malats, M Büchler, M Pajic, AV Biankin, J Iovanna, J Neoptolemos, FX Real. GATA6 regulates EMT and tumour dissemination, and is a marker of response to adjuvant chemotherapy in pancreatic cancer. Gut 2017; 66(9): 1665–1676 https://doi.org/10.1136/gutjnl-2015-311256 pmid: 27325420
13	AA Ganaie, FH Beigh, M Astone, MG Ferrari, R Maqbool, S Umbreen, AS Parray, HR Siddique, T Hussain, P Murugan, C Morrissey, S Koochekpour, Y Deng, BR Konety, LH Hoeppner, M Saleem. BMI1 drives metastasis of prostate cancer in Caucasian and African-American men and is a potential therapeutic target: hypothesis tested in race-specific models. Clin Cancer Res 2018; 24(24): 6421–6432 https://doi.org/10.1158/1078-0432.CCR-18-1394 pmid: 30087142
14	EN Kouwenhoven, Heeringen SJ van, JJ Tena, M Oti, BE Dutilh, ME Alonso, la Calle-Mustienes E de, L Smeenk, T Rinne, L Parsaulian, E Bolat, R Jurgelenaite, MA Huynen, A Hoischen, JA Veltman, HG Brunner, T Roscioli, E Oates, M Wilson, M Manzanares, JL Gómez-Skarmeta, HG Stunnenberg, M Lohrum, Bokhoven H van, H Zhou. Genome-wide profiling of p63 DNA-binding sites identifies an element that regulates gene expression during limb development in the 7q21 SHFM1 locus. PLoS Genet 2010; 6(8): e1001065 https://doi.org/10.1371/journal.pgen.1001065 pmid: 20808887
15	C Lu, D Yang, ME Sabbatini, AH Colby, MW Grinstaff, NH Oberlies, C Pearce, K Liu. Contrasting roles of H3K4me3 and H3K9me3 in regulation of apoptosis and gemcitabine resistance in human pancreatic cancer cells. BMC Cancer 2018; 18(1): 149 https://doi.org/10.1186/s12885-018-4061-y pmid: 29409480
16	X Hu, C Feng, Y Zhou, A Harrison, M Chen. DeepTrio: a ternary prediction system for protein-protein interaction using mask multiple parallel convolutional neural networks. Bioinformatics 2021; 38(3): 694–702 https://doi.org/10.1093/bioinformatics/btab737 pmid: 34694333
17	T Sakamoto, J S Weng, T Hara, S Yoshino, H Kozuka-Hata, M Oyama, M Seiki. Hypoxia-inducible factor 1 regulation through cross talk between mTOR and MT1-MMP. Mol Cell Biol. 2014; 34(1): 30–42 https://doi.org/10.1128/MCB.01169-13 pmid: 24164895
18	X Li, A Eberhardt, JN Hansen, D Bohmann, H Li, NF Schor. Methylation of the phosphatase-transcription activator EYA1 by protein arginine methyltransferase 1: mechanistic, functional, and structural studies. FASEB J 2017; 31(6): 2327–2339 https://doi.org/10.1096/fj.201601050RR pmid: 28213359
19	R SantamariaG EspositoL VitaglianoV RaceI PaglionicoL ZancanA ZagariF Salvatore. Functional and molecular modelling studies of two hereditary fructose intolerance-causing mutations at arginine 303 in human liver aldolase. Biochem J 2000; 350 Pt 3(Pt 3): 823–828
20	Y Zhang, MH Heinsen, M Kostic, GM Pagani, TV Riera, I Perovic, L Hedstrom, BB Snider, TC Pochapsky. Analogs of 1-phosphonooxy-2,2-dihydroxy-3-oxo-5-(methylthio)pentane, an acyclic intermediate in the methionine salvage pathway: a new preparation and characterization of activity with E1 enolase/phosphatase from Klebsiella oxytoca. Bioorg Med Chem 2004; 12(14): 3847–3855 https://doi.org/10.1016/j.bmc.2004.05.002 pmid: 15210152
21	AR Deshpande, K Wagenpfeil, TC Pochapsky, GA Petsko, D Ringe. Metal-dependent function of a mammalian acireductone dioxygenase. Biochemistry 2016; 55(9): 1398–1407 https://doi.org/10.1021/acs.biochem.5b01319 pmid: 26858196
22	J Wang, M Tan, J Ge, P Zhang, J Zhong, L Tao, Q Wang, X Tong, J Qiu. Lysosomal acid lipase promotes cholesterol ester metabolism and drives clear cell renal cell carcinoma progression. Cell Prolif 2018; 51(4): e12452 https://doi.org/10.1111/cpr.12452 pmid: 29569766
23	BS AlexandrovFL IlievV Stanev V VesselinovLB Alexandrov. rNMF 1.0: Robust Nonnegative matrix factorization with kmeans clustering and signal shift. 2016
24	J Guinney, R Dienstmann, X Wang, Reyniès A de, A Schlicker, C Soneson, L Marisa, P Roepman, G Nyamundanda, P Angelino, BM Bot, JS Morris, IM Simon, S Gerster, E Fessler, Sousa E Melo F De, E Missiaglia, H Ramay, D Barras, K Homicsko, D Maru, GC Manyam, B Broom, V Boige, B Perez-Villamil, T Laderas, R Salazar, JW Gray, D Hanahan, J Tabernero, R Bernards, SH Friend, P Laurent-Puig, JP Medema, A Sadanandam, L Wessels, M Delorenzi, S Kopetz, L Vermeulen, S Tejpar, S Tejpar. The consensus molecular subtypes of colorectal cancer. Nat Med 2015; 21(11): 1350–1356 https://doi.org/10.1038/nm.3967 pmid: 26457759
25	X He, M Li, H Yu, G Liu, N Wang, C Yin, Q Tu, G Narla, Y Tao, S Cheng, H Yin, H Yin. Loss of hepatic aldolase B activates Akt and promotes hepatocellular carcinogenesis by destabilizing the Aldob/Akt/PP2A protein complex. PLoS Biol 2020; 18(12): e3000803 https://doi.org/10.1371/journal.pbio.3000803 pmid: 33275593
26	K Takayama, T Suzuki, T Fujimura, T Urano, S Takahashi, Y Homma, S Inoue. CtBP2 modulates the androgen receptor to promote prostate cancer progression. Cancer Res 2014; 74(22): 6542–6553 https://doi.org/10.1158/0008-5472.CAN-14-1030 pmid: 25228652
27	DP Wang, LL Gu, Q Xue, H Chen, GX Mao. CtBP2 promotes proliferation and reduces drug sensitivity in non-small cell lung cancer via the Wnt/β-catenin pathway. Neoplasma 2018; 65(6): 888–897 https://doi.org/10.4149/neo_2018_171220N828 pmid: 30334447
28	S Paliwal, N Ho, D Parker, SR Grossman. CtBP2 promotes human cancer cell migration by transcriptional activation of tiam1. Genes Cancer 2012; 3(7–8): 481–490 https://doi.org/10.1177/1947601912463695 pmid: 23264848
29	F Dai, Y Xuan, JJ Jin, S Yu, ZW Long, H Cai, XW Liu, Y Zhou, YN Wang, Z Chen, H Huang. CtBP2 overexpression promotes tumor cell proliferation and invasion in gastric cancer and is associated with poor prognosis. Oncotarget 2017; 8(17): 28736–28749 https://doi.org/10.18632/oncotarget.15661 pmid: 28404932
30	KGR Quinlan, A Verger, A Kwok, SHY Lee, J Perdomo, M Nardini, M Bolognesi, M Crossley. Role of the C-terminal binding protein PXDLS motif binding cleft in protein interactions and transcriptional repression. Mol Cell Biol 2006; 26(21): 8202–8213 https://doi.org/10.1128/MCB.00445-06 pmid: 16940173
31	GM Riefler, BL Firestein. Binding of neuronal nitric-oxide synthase (nNOS) to carboxyl-terminal-binding protein (CtBP) changes the localization of CtBP from the nucleus to the cytosol: a novel function for targeting by the PDZ domain of nNOS. J Biol Chem 2001; 276(51): 48262–48268 https://doi.org/10.1074/jbc.M106503200 pmid: 11590170
32	B Benziane, S Demaretz, N Defontaine, N Zaarour, L Cheval, S Bourgeois, C Klein, M Froissart, A Blanchard, M Paillard, G Gamba, P Houillier, K Laghmani. NKCC2 surface expression in mammalian cells: down-regulation by novel interaction with aldolase B. J Biol Chem 2007; 282(46): 33817–33830 https://doi.org/10.1074/jbc.M700195200 pmid: 17848580
33	LJ Zhao, M Kuppuswamy, S Vijayalingam, G Chinnadurai. Interaction of ZEB and histone deacetylase with the PLDLS-binding cleft region of monomeric C-terminal binding protein 2. BMC Mol Biol 2009; 10(1): 89 https://doi.org/10.1186/1471-2199-10-89 pmid: 19754958
34	M Lu, D Ammar, H Ives, F Albrecht, SL Gluck. Physical interaction between aldolase and vacuolar H+-ATPase is essential for the assembly and activity of the proton pump. J Biol Chem 2007; 282(34): 24495–24503 https://doi.org/10.1074/jbc.M702598200 pmid: 17576770
35	S Lee, S Hong, S Kim, S Kang. Ataxin-1 occupies the promoter region of E-cadherin in vivo and activates CtBP2-repressed promoter. Biochim Biophys Acta 2011; 1813(5): 713–722 https://doi.org/10.1016/j.bbamcr.2011.01.035 pmid: 21315774
36	C Wan, B Borgeson, S Phanse, F Tu, K Drew, G Clark, X Xiong, O Kagan, J Kwan, A Bezginov, K Chessman, S Pal, G Cromar, O Papoulas, Z Ni, DR Boutz, S Stoilova, PC Havugimana, X Guo, RH Malty, M Sarov, J Greenblatt, M Babu, WB Derry, ER Tillier, JB Wallingford, J Parkinson, EM Marcotte, A Emili. Panorama of ancient metazoan macromolecular complexes. Nature 2015; 525(7569): 339–344 https://doi.org/10.1038/nature14877 pmid: 26344197
37	G Lucarelli, D Loizzo, R Franzin, S Battaglia, M Ferro, F Cantiello, G Castellano, C Bettocchi, P Ditonno, M Battaglia. Metabolomic insights into pathophysiological mechanisms and biomarker discovery in clear cell renal cell carcinoma. Expert Rev Mol Diagn 2019; 19(5): 397–407 https://doi.org/10.1080/14737159.2019.1607729 pmid: 30983433
38	R Ragone, F Sallustio, S Piccinonna, M Rutigliano, G Vanessa, S Palazzo, G Lucarelli, P Ditonno, M Battaglia, FP Fanizzi, FP Schena. Renal cell carcinoma: a study through NMR-based metabolomics combined with transcriptomics. Diseases 2016; 4(1): 7 https://doi.org/10.3390/diseases4010007 pmid: 28933387
39	C Bianchi, C Meregalli, S Bombelli, V Di Stefano, F Salerno, B Torsello, S De Marco, G Bovo, I Cifola, E Mangano, C Battaglia, G Strada, G Lucarelli, RH Weiss, RA Perego. The glucose and lipid metabolism reprogramming is grade-dependent in clear cell renal cell carcinoma primary cultures and is targetable to modulate cell viability and proliferation. Oncotarget 2017; 8(69): 113502–113515 https://doi.org/10.18632/oncotarget.23056 pmid: 29371925
40	G Lucarelli, M Ferro, D Loizzo, C Bianchi, D Terracciano, F Cantiello, LN Bell, S Battaglia, C Porta, A Gernone, RA Perego, E Maiorano, O Cobelli, G Castellano, L Vincenti, P Ditonno, M Battaglia. Integration of lipidomics and transcriptomics reveals reprogramming of the lipid metabolism and composition in clear cell renal cell carcinoma. Metabolites 2020; 10(12): 509 https://doi.org/10.3390/metabo10120509 pmid: 33322148
41	S Bombelli, B Torsello, S De Marco, G Lucarelli, I Cifola, C Grasselli, G Strada, G Bovo, RA Perego, C Bianchi. 36-kDa annexin A3 isoform negatively modulates lipid storage in clear cell renal cell carcinoma cells. Am J Pathol 2020; 190(11): 2317–2326 https://doi.org/10.1016/j.ajpath.2020.08.008 pmid: 32861643
42	G Lucarelli, M Rutigliano, F Sallustio, D Ribatti, A Giglio, M Lepore Signorile, V Grossi, P Sanese, A Napoli, E Maiorano, C Bianchi, RA Perego, M Ferro, E Ranieri, G Serino, LN Bell, P Ditonno, C Simone, M Battaglia. Integrated multi-omics characterization reveals a distinctive metabolic signature and the role of NDUFA4L2 in promoting angiogenesis, chemoresistance, and mitochondrial dysfunction in clear cell renal cell carcinoma. Aging (Albany NY) 2018; 10(12): 3957–3985 https://doi.org/10.18632/aging.101685 pmid: 30538212
43	F Gatto, I Nookaew, J Nielsen. Chromosome 3p loss of heterozygosity is associated with a unique metabolic network in clear cell renal carcinoma. Proc Natl Acad Sci USA 2014; 111(9): E866–E875 https://doi.org/10.1073/pnas.1319196111 pmid: 24550497
44	B Li, B Qiu, DSM Lee, ZE Walton, JD Ochocki, LK Mathew, A Mancuso, TPF Gade, B Keith, I Nissim, MC Simon. Fructose-1,6-bisphosphatase opposes renal carcinoma progression. Nature 2014; 513(7517): 251–255 https://doi.org/10.1038/nature13557 pmid: 25043030
45	QF Tao, SX Yuan, F Yang, S Yang, Y Yang, JH Yuan, ZG Wang, QG Xu, KY Lin, J Cai, J Yu, WL Huang, XL Teng, CC Zhou, F Wang, SH Sun, WP Zhou. Aldolase B inhibits metastasis through ten-eleven translocation 1 and serves as a prognostic biomarker in hepatocellular carcinoma. Mol Cancer 2015; 14(1): 170 https://doi.org/10.1186/s12943-015-0437-7 pmid: 26376879
46	J Lian, L Xia, Y Chen, J Zheng, K Ma, L Luo, F Ye. Aldolase B impairs DNA mismatch repair and induces apoptosis in colon adenocarcinoma. Pathol Res Pract 2019; 215(11): 152597 https://doi.org/10.1016/j.prp.2019.152597 pmid: 31564566
47	P Bu, KY Chen, K Xiang, C Johnson, SB Crown, N Rakhilin, Y Ai, L Wang, R Xi, I Astapova, Y Han, J Li, BB Barth, M Lu, Z Gao, R Mines, L Zhang, M Herman, D Hsu, GF Zhang, X Shen. Aldolase B-mediated fructose metabolism drives metabolic reprogramming of colon cancer liver metastasis. Cell Metab 2018; 27(6): 1249–1262.e4 https://doi.org/10.1016/j.cmet.2018.04.003 pmid: 29706565
48	M Li, CS Zhang, Y Zong, JW Feng, T Ma, M Hu, Z Lin, X Li, C Xie, Y Wu, D Jiang, Y Li, C Zhang, X Tian, W Wang, Y Yang, J Chen, J Cui, YQ Wu, X Chen, QF Liu, J Wu, SY Lin, Z Ye, Y Liu, HL Piao, L Yu, Z Zhou, XS Xie, DG Hardie, SC Lin. Transient receptor potential V channels are essential for glucose sensing by aldolase and AMPK. Cell Metab 2019; 30(3): 508–524.e12 https://doi.org/10.1016/j.cmet.2019.05.018 pmid: 31204282
49	G Liu, N Wang, C Zhang, M Li, X He, C Yin, Q Tu, X Shen, L Zhang, J Lv, Y Wang, H Jiang, S Chen, N Li, Y Tao, H Yin. Fructose-1,6-bisphosphate aldolase B depletion promotes hepatocellular carcinogenesis through activating insulin receptor signaling and lipogenesis. Hepatology 2021; 74(6): 3037–3055 https://doi.org/10.1002/hep.32064 pmid: 34292642
50	CB Chan, X Liu, SW Jang, SIH Hsu, I Williams, S Kang, J Chen, K Ye. NGF inhibits human leukemia proliferation by downregulating cyclin A1 expression through promoting acinus/CtBP2 association. Oncogene 2009; 28(43): 3825–3836 https://doi.org/10.1038/onc.2009.236 pmid: 19668232
51	L Barroilhet, J Yang, K Hasselblatt, RM Paranal, SK Ng, JA Rauh-Hain, WR Welch, JE Bradner, RS Berkowitz, SW Ng. C-terminal binding protein-2 regulates response of epithelial ovarian cancer cells to histone deacetylase inhibitors. Oncogene 2013; 32(33): 3896–3903 https://doi.org/10.1038/onc.2012.380 pmid: 22945647
52	L Wang, H Zhou, Y Wang, G Cui, LJ Di. CtBP maintains cancer cell growth and metabolic homeostasis via regulating SIRT4. Cell Death Dis 2015; 6(1): e1620 https://doi.org/10.1038/cddis.2014.587 pmid: 25633289
53	CC Fjeld, WT Birdsong, RH Goodman. Differential binding of NAD+ and NADH allows the transcriptional corepressor carboxyl-terminal binding protein to serve as a metabolic sensor. Proc Natl Acad Sci USA 2003; 100(16): 9202–9207 https://doi.org/10.1073/pnas.1633591100 pmid: 12872005

[1]

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