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RACK1 forms a complex with FGFR1 and PKM2, and stimulates the growth and migration of squamous lung cancer cells
Author(s) -
Zhou Chengzhi,
Chen Tao,
Xie Zhanhong,
Qin Yinyin,
Ou Yangming,
Zhang Jiexia,
Li Shiyue,
Chen Rongchang,
Zhong Nanshan
Publication year - 2017
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22663
Subject(s) - biology , cancer research , lung cancer , carcinogenesis , pkm2 , fibroblast growth factor receptor 1 , fibroblast growth factor , cancer , signal transduction , microbiology and biotechnology , receptor , medicine , biochemistry , pyruvate kinase , genetics , glycolysis , enzyme
Phosphorylation of Pyruvate Kinase M2 (PKM2) on Tyr105 by fibroblast growth factor receptor 1 (FGFR1) has been shown to promote its nuclear localization as well as cell growth in lung cancer. Better understanding the regulation of this process would benefit the clinical treatment for lung cancer. Here, it has been found that the adaptor protein receptor for activated PKC kinase (RACK1) formed a complex with FGFR1 and PKM2, and activated the FGFR1/PKM2 signaling. Knocking down the expression of RACK1 impaired the phosphorylation on Tyr105 of PKM2 and inhibited the growth and migration of lung cancer cells, while over‐expression of RACK1 in lung cancer cells led to the resistance to Erdafitinib. Moreover, knocking down the expression of RACK1 impaired the tumorigenesis of lung cancer driven by LKB loss and mutated Ras (KrasG12D). Taken together, our study demonstrated the pivotal roles of RACK1 in FGFR1/PKM2 signaling, suggesting FGFR1/RACK1/PKM2 might be a therapeutic target for lung cancer treatment.