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Published on: July 20, 2019
TNF antagonizes CCN1 in apoptosis in esophageal adenocarcinoma
Tong Dang1, Zhiheng Chang1, Jing Meng1
1Inner 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.
Abstract:
TNF signaling mostly supports cell growth by activating NFκB and only induces cell death when NFκB activation fails. CCN1 is a matricellular protein that has been reported capable to convert TNF from a pro-survival factor into a stimulus for cell death without interfering with NFκB signaling. In this study, we examined the relationship between CCN1 and TNF in the context of esophageal adenocarcinoma and found that CCN1 did not help TNF to induce cell death when they were together, instead, it inhibited TNF expression, as well as TNF-induced JNK activation and apoptosis. CCN1 induced apoptosis in the cancer cells by itself through upregulation of TRAIL and its death receptors. The presence of TNF significantly lowered CCN1 expression and its capability in apoptosis induction. Furthermore, we found that CCN1 boosted ADAM17-mediated cleavage of TNF receptors through ITGA11 and the soluble decoy receptors generated by this action neutralized TNF activity. Taken together, CCN1 and TNF antagonize each other in esophageal cancer cells.
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