PT - JOURNAL ARTICLE AU - Chen, Tao AU - Wang, Fei AU - Wei, Shupei AU - Nie, Yingjie AU - Zheng, Xiaotao AU - Deng, Yu AU - Zhu, Xubin AU - Deng, Yuezhen AU - Zhong, Nanshan AU - Zhou, Chengzhi TI - FGFR/RACK1 interacts with MDM2, promotes P53 degradation, and inhibits cell senescence in lung squamous cell carcinoma AID - 10.20892/j.issn.2095-3941.2020.0389 DP - 2021 Aug 01 TA - Cancer Biology and Medicine PG - 665--674 VI - 18 IP - 3 4099 - http://www.cancerbiomed.org/content/18/3/665.short 4100 - http://www.cancerbiomed.org/content/18/3/665.full SO - Cancer Biol Med2021 Aug 01; 18 AB - Objective: FGFR is considered an important driver gene of lung squamous cell carcinoma (LSCC). Thus, identification of the biological events downstream of FGFR is important for the treatment of this malignancy. Our previous study has shown that the FGFR/RACK1 complex interacts with PKM2 and consequently promotes glycolysis in LSCC cells. However, the biological functions of the FGFR/RACK1 complex remain poorly understood.Methods: Anchorage-independent assays and in vivo tumorigenesis assays were performed to evaluate cancer cell malignancy. Distant seeding assays were performed to evaluate cancer cell metastasis. β-gal staining was used to examine cell senescence, and immunoprecipitation assays were performed to examine the interactions among FGFR, RACK1, and MDM2.Results: FGFR/RACK1 was found to regulate the senescence of LSCC cells. Treatment with PD166866, an inhibitor of FGFR, or knockdown of RACK1 induced senescence in LSCC cells (P < 0.01). A molecular mechanistic study showed that FGFR/RACK1/MDM2 form a complex that promotes the degradation of p53 and thus inhibits cell senescence. PD166866 and RG7112, an MDM2/p53 inhibitor, cooperatively inhibited the colony formation and distal seeding of LSCC cells (P < 0.01), and upregulated the expression of p53 and p21.Conclusions: Together, our findings revealed the regulatory roles and mechanisms of FGFR/RACK1 in cell senescence. This understanding should be important in the treatment of LSCC.