B7-H3 suppresses doxorubicin-induced senescence-like growth arrest in colorectal cancer through the AKT/TM4SF1/SIRT1 pathway.

Ruoqin Wang, Linqing Sun, Suhua Xia, Hongya Wu, Yanchao Ma, Shenghua Zhan, Guangbo Zhang, Xueguang Zhang, Tongguo Shi, Weichang Chen

Cell death & disease 2021 May 06

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Emerging evidence suggests that cellular senescence induced by chemotherapy has been recognized as a new weapon for cancer therapy. This study aimed to research novel functions of B7-H3 in cellular senescence induced by a low dose of doxorubicin (DOX) in colorectal cancer (CRC). Here, our results demonstrated that B7-H3 knockdown promoted, while B7-H3 overexpression inhibited, DOX-induced cellular senescence. B7-H3 knockdown dramatically enhanced the growth arrest of CRC cells after low-dose DOX treatment, but B7-H3 overexpression had the opposite effect. By RNA-seq analysis and western blot, we showed that B7-H3 prevented cellular senescence and growth arrest through the AKT/TM4SF1/SIRT1 pathway. Blocking the AKT/TM4SF1/SIRT1 pathway dramatically reversed B7-H3-induced resistance to cellular senescence. More importantly, B7-H3 inhibited DOX-induced cellular senescence of CRC cells in vivo. Therefore, targeting B7-H3 or the B7-H3/AKT/TM4SF1/SIRT1 pathway might be a new strategy for promoting cellular senescence-like growth arrest during drug treatment in CRC.

Citation

Ruoqin Wang, Linqing Sun, Suhua Xia, Hongya Wu, Yanchao Ma, Shenghua Zhan, Guangbo Zhang, Xueguang Zhang, Tongguo Shi, Weichang Chen. B7-H3 suppresses doxorubicin-induced senescence-like growth arrest in colorectal cancer through the AKT/TM4SF1/SIRT1 pathway. Cell death & disease. 2021 May 06;12(5):453