RT Journal Article
SR Electronic
T1 FGFR/RACK1 interacts with MDM2, promotes P53 degradation, and inhibits cell senescence in lung squamous cell carcinoma
JF Cancer Biology and Medicine
JO Cancer Biol Med
FD China Anti-Cancer Association
SP 665
OP 674
DO 10.20892/j.issn.2095-3941.2020.0389
VO 18
IS 3
A1 Tao Chen
A1 Fei Wang
A1 Shupei Wei
A1 Yingjie Nie
A1 Xiaotao Zheng
A1 Yu Deng
A1 Xubin Zhu
A1 Yuezhen Deng
A1 Nanshan Zhong
A1 Chengzhi Zhou
YR 2021
UL http://www.cancerbiomed.org/content/18/3/665.abstract
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.