Potential functions of esophageal cancer-related gene-4 in the cardiovascular system

Abstract

Esophageal cancer-related gene-4 (Ecrg4) is cloned from the normal epithelium of the esophagus. It is constitutively expressed in quiescent epithelial cells and downregulated during tumorigenesis, and Ecrg4 expression levels are inversely correlated with the malignant phenotype of tumor cells, validating that Ecrg4 is a real tumor suppressor gene. Unlike other tumor suppressor genes that usually encode membrane or intracellular proteins, Ecrg4 encodes a 148-amino acid pre-pro-peptide that is tethered on the cell surface in epithelial cells, specialized epithelial cells, and human leukocytes, where it can be processed tissue dependently into several small peptides upon cell activation. Ecrg4 is expressed in a wide variety of other cells/tissues, including cardiomyocytes and conduction system of the heart，, the glomus cells of the carotid body, adrenal glands, choroid plexus, and leukocytes among others, where it exerts distinct functions, such as promoting/suppressing inflammation, inducing neuron senescence, stimulating the hypothalamus--pituitary--adrenal axis, maintaining the stemness of stem cells, participating in the rhythm and rate control of the heart, and possibly gauging the responsiveness of the cardiovascular system (CVS) to hypoxia, in addition to tumor suppression. Here, we briefly review the latest discoveries on Ecrg4 and its underlying molecular mechanisms as a tumor suppressor and focus on the emerging roles of Ecrg4 in the CVS.

Keywords

tumor suppressor gene / esophageal cancer-related gene-4 / cardiovascular disease, hypoxia

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Acknowledgements

This study was funded by the Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Southwest Medical University (No. xtcx-2016-16), the National Natural Science Foundation of China (No. 81770336), and a seeding grant from Southwest Medical University.

Compliance with ethics guidelines

Rui Zhou, Yuanshu Liu, Wenjun Huang, and Xitong Dang declared that they have no conflict of interest to disclose. This manuscript is a review article and does not involve a research protocol requiring approval by a relevant institutional review board or ethics committee.

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