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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

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Front. Med.    2019, Vol. 13 Issue (5) : 540-546    https://doi.org/10.1007/s11684-018-0637-9
REVIEW
ECRG4: a new potential target in precision medicine
Xin Qin1, Ping Zhang2()
1. Medical College, Hubei University of Arts and Science, Xiangyang 441053, China
2. State Key Laboratory of Cancer Biology, Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi’an 710032, China
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Abstract

Given the rapid development in precision medicine, tremendous efforts have been devoted to discovering new biomarkers for disease diagnosis and treatment. Esophageal cancer-related gene-4 (ECRG4), which is initially known as a new candidate tumor suppressor gene, is emerging as a sentinel molecule for gauging tissue homeostasis. ECRG4 is unique in its cytokine-like functional pattern and epigenetically-regulated gene expression pattern. The gene can be released from the cell membrane upon activation and detected in liquid biopsy, thus offering considerable potential in precision medicine. This review provides an updated summary on the biology of ECRG4, with emphasis on its important roles in cancer diagnosis and therapy. The future perspectives of ECRG4 as a potential molecular marker in precision medicine are also discussed in detail.
Keywords ECRG4      tumor suppressor gene      sentinel molecule      precision medicine      cell senescence      epithelium homeostasis     
Corresponding Author(s): Ping Zhang   
Just Accepted Date: 10 May 2018   Online First Date: 12 July 2018    Issue Date: 14 October 2019
 Cite this article:   
Xin Qin,Ping Zhang. ECRG4: a new potential target in precision medicine[J]. Front. Med., 2019, 13(5): 540-546.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-018-0637-9
https://academic.hep.com.cn/fmd/EN/Y2019/V13/I5/540
Fig.1  Processing of ECRG4 protein. The ECRD4 gene encodes a 148-amino-acid (aa) protein that consists of 30-aa leader sequence and 14 kDa augurin. ECRG4 presumably contains two consensus protease cleavage sites. One furin-like cleavage site is located at 68–71, and the other thrombin consensus cleavage site is located at 130–134. ECRG4 processing from furin-like cleavage site may yield two peptides, namely, ecilin (4 kDa) and argilin (8 kDa); processing from the thrombin consensus cleavage site may yield three peptides, namely, CD16, CD16-augurin, and CD16-argilin.
Fig.2  Roles of ECRG4 in vivo and its underling molecular mechanism. After binding to undefined ligands on the cell membrane, ECRG4 stimulates downstream cascades to affect cell proliferation or G1 cell cycle arrest by employing p53 pathway or inhibiting NF-κB-COX-2 signaling pathway. ECRG4 plays important roles in cancer, cell senescence, homeostasis guarding, and immunity and other undiscovered functions represented by “?”.
Cell line name Cell source Regulation of ECRG4 Impacts of ECRG4 References
HCT116 and SW480 Colorectal cell lines ECRG4↑ Cell proliferation↓
Cell viability ↓		 [25]
SW480 and Caco-2 Colorectal cell lines ECRG4↑ Cell proliferation↓
Cell apoptosis↑		 [26]
M2 cell Head and neck cells ECRG4↑ Proliferation ↓
Cell cycle arrest ↑
Apoptosis↑		 [27]
Hep-2 and LSC-1 Human laryngeal cancer ?cell lines ECRG4↑ Cell proliferation↓
Cell cycle arrested in G0/G1↑		 [28]
BT549 and MDAMB231 Breast cancer ECRG4↑ Proliferation↓
Migration and invasion↓		 [29]
SKBR3 and MDAMB468 Breast cancer ECRG4↓ Growth↑
Invasion↑		 [29]
U251 Glioma cells ECRG4↑ Proliferation and inhibition of ?cell migration and cell cycle ?progression ↓ [30]
SGC-7901 Gastric cell line ECRG4↑ Apoptosis↑
Sensitivity to 5-FU↑		 [4]
CNE1 cell line Human nasopharyngeal ?cancer cells ECRG4↑ Cell growth rate↓
Sensitivity to cisplatin↑		 [40]
Tab.1  Functions of ECRG4 in cancer cells
Cancer type Expression of ECRG4 Clinic significance References
Esophageal carcinoma ECRG4↓
or none		 Related to the degree of tumor invasion level, TNM ?staging, lymph node metastasis, and recurrence and ?survival after surgery [33]
Breast cancer ECRG4↓ Related to the tumor stage, tumor volume, risk of ?distant metastasis, survival rate, and overall survival ?time [34,35]
Prostate cancer ECRG4↓ Prostate-specific antigen recurrence
Histology differentiation and lymph node metastasis		 [36]
Gastric cancer ECRG4↓ Cancer stages [37]
Nasopharyngeal carcinoma ECRG4↓ Correlated with lymph node metastasis and predicts ?poor outcome [38]
Renal cell cancer ECRG4↓ Associated with poor prognosis [39]
Tab.2  Clinic significances of ECRG4 in cancer
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