CCN1 suppresses cell proliferation of esophageal squamous cell carcinoma through amyloid precursor protein without DR6 participation

Pei Wang; Zhiheng Chang; Jing Meng; Xia Cui; Jianyuan Chai; Tong Dang

doi:10.1016/j.cellsig.2022.110374

CCN1 suppresses cell proliferation of esophageal squamous cell carcinoma through amyloid precursor protein without DR6 participation

Cell Signal. 2022 Aug:96:110374. doi: 10.1016/j.cellsig.2022.110374. Epub 2022 May 30.

Authors

Pei Wang¹, Zhiheng Chang¹, Jing Meng¹, Xia Cui¹, Jianyuan Chai², Tong Dang³

Affiliations

¹ Inner Mongolia Institute of Digestive Diseases, Inner Mongolia Engineering Research Center for Prevention and Treatment of Digestive Diseases, The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, 30 Hudemulin Rd, Baotou 014030, China.
² Inner Mongolia Institute of Digestive Diseases, Inner Mongolia Engineering Research Center for Prevention and Treatment of Digestive Diseases, The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, 30 Hudemulin Rd, Baotou 014030, China. Electronic address: Jianyuan.chai@gmail.com.
³ Inner Mongolia Institute of Digestive Diseases, Inner Mongolia Engineering Research Center for Prevention and Treatment of Digestive Diseases, The Second Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, 30 Hudemulin Rd, Baotou 014030, China. Electronic address: 15947623515@163.com.

PMID: 35654297
DOI: 10.1016/j.cellsig.2022.110374

Abstract

Esophageal cancer is commonly seen as either squamous cell carcinoma (ESCC) or adenocarcinoma (EAC), two very different cancers. CCN1 is a matricellular protein that induces apoptosis in EAC cells through upregulation of DR5, a death receptor, while its role in ESCC is unclear. DR6 is another death receptor, which has been reported to induce apoptosis, necroptosis, or pyroptosis in various cell systems with or without the engagement of its putative ligand amyloid precursor protein (APP). In this study, we found that CCN1 and DR6 were both highly expressed in ESCC but downregulated in EAC. Overexpression of CCN1 in ESCC cells inhibited cell proliferation through upregulation of APP and its association with p53 without DR6 involvement. Overexpression of APP stopped cell growth, but overexpression of DR6 did not affect cell growth or cell death whatsoever.

Keywords: APP; CCN1; Cell growth; DR6; Esophageal cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyloid beta-Protein Precursor / metabolism
Apoptosis
Cell Line, Tumor
Cell Proliferation
Esophageal Neoplasms* / metabolism
Esophageal Squamous Cell Carcinoma*
Humans
Receptors, Death Domain

Substances

Amyloid beta-Protein Precursor
Receptors, Death Domain