The Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, China
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.
Matsuzaki, J., et al. Carcinogenesis 2012; 33(5): 996–1003 [31].
Inhibition of neuronal stem cell proliferation
Nakatani, Y., et al. Development 2019; 146 (4): dev168120 [38].
In CVS
Ecrg4 in the carotid body (gene microarray)
Balbir, A., et al. Am J Physiol Lung Cell Mol Physiol. 2007; 292 (3): ?L704–L715 [15].
Ecrg4 expression in the A-V node (in situ)
Mirabeau, O., et al. Genome Res. 2007; 17(3): 320–327 [32].
Ecrg4 expression in cardiomyocytes of rat (IHC)
Porzionato, A., et al. Eur J Histochem. 2015; 18; 59 (2): 2458 [7].
Distribution of Ecrg4 in rat heart (IHC and qPCR), in specimens ?of atria in patients with AFib. (IHC), and in canine model of ?AFib. (qPCR). Involved in AFib.
Huang, L. et al. Sci Rep. 2017; 7(1): 2717 [5].
Tab.1
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