FBXL2 counteracts Grp94 to destabilize EGFR and inhibit EGFR-driven NSCLC growth.
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ABSTRACT:
SUBMITTER: Niu M
PROVIDER: S-EPMC8505509 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
Publications
FBXL2 counteracts Grp94 to destabilize EGFR and inhibit EGFR-driven NSCLC growth.
Niu Mengmeng M Xu Jing J Liu Yang Y Li Yuhuang Y He Tao T Ding Liangping L He Yajun Y Yi Yong Y Li Fengtian F Guo Rongtian R Gao Ya Y Li Rui R Li Luping L Fu Mengyuan M Hu Qingyong Q Luo Yangkun Y Zhang Chunyan C Qin Kewei K Yi Jianqiao J Yu Shuhan S Yang Jian J Chen Hu H Wang Liang L Li Zhonghan Z Dong Biao B Qi Shiqian S Ouyang Liang L Zhang Yujun Y Cao Yang Y Xiao Zhi-Xiong Jim ZJ
Nature communications 20211011 1
Abnormal activation of epidermal growth factor receptor (EGFR) drives non-small cell lung cancer (NSCLC) development. EGFR mutations-mediated resistance to tyrosine-kinase inhibitors (TKIs) is a major hurdle for NSCLC treatment. Here, we show that F-box protein FBXL2 targets EGFR and EGFR TKI-resistant mutants for proteasome-mediated degradation, resulting in suppression of EGFR-driven NSCLC growth. Reduced FBXL2 expression is associated with poor clinical outcomes of NSCLC patients. Furthermore ...[more]
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