CD142 plays a key role in the carcinogenesis of gastric adenocarcinoma by inhibiting BCL2-dependent autophagy.

Weifeng Xu, Beibei Chen, Dianshan Ke, Xiaobing Chen

Biochemistry and cell biology = Biochimie et biologie cellulaire 2022 Feb

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CD142 is expressed on the surface of multiple malignant tumors and contributes to carcinogenesis. However, the role of CD142 in the pathogenesis of gastric adenocarcinoma (GAC) remains unclear. This study aimed to investigate the role of CD142 in GAC carcinogenesis. Our results showed that CD142 expression was significantly increased in GAC cancer tissues, especially in those with significant invasion or metastasis. The invasion and migration of CD142-positive SNU16 cells was significantly increased compared to that of CD142-negative cells. Moreover, CD142 overexpression promoted the invasion and migration of SGC083 cells, but CD142 silencing had the opposite effect. In addition, there was a positive correlation between CD142 expression in cancer tissues and serum Interleukin-8 (IL-8) levels. CD142 overexpression promoted IL-8 production in SGC083 cells. In vivo analysis showed that the implantation of CD142-positive SNU16 cells promoted the growth of xenograft tumor and the production of IL-8. Mechanistically, CD142 silencing not only inhibited the expression of BCL2 and the interaction between BCL2 and Beclin1, but also promoted the autophagic response in SGC083. Furthermore, CD142 silencing-induced IL-8 degradation was recovered by treatment with the autophagy inhibitor, 3-MA. CD142 can inhibit autophagic cell death and autophagic degradation of IL-8 in GAC, which exerts an effect on GAC carcinogenesis.

Citation

Weifeng Xu, Beibei Chen, Dianshan Ke, Xiaobing Chen. CD142 plays a key role in the carcinogenesis of gastric adenocarcinoma by inhibiting BCL2-dependent autophagy. Biochemistry and cell biology = Biochimie et biologie cellulaire. 2022 Feb;100(1):17-27