EGF-induced nuclear localization of SHCBP1 activates β-catenin signaling and promotes cancer progression

作者：Lei Liu, Yi Yang, Zhongshu Li, Tianyu Tao, Junchao Cai, Jueheng Wu, Hongyu Guan, Xun Zhu, Zhenjian He, Jun Li, Erwei Song, Mu‐Sheng Zeng, Mengfeng Li · 发表于：Oncogene · 年份：2018 · DOI：10.1038/s41388-018-0473-z · 被引用次数：63 · 研究领域：Cancer-related gene regulation、Wnt/β-catenin signaling in development and cancer、Ubiquitin and proteasome pathways

Aberrant activation of EGFR represents a common event in non-small cell lung carcinoma (NSCLC) and activates various downstream signaling pathways. While EGFR activation of β-catenin signaling was previously reported, the mediating mechanism remains unclear. Our current study found that EGFR activation in NSCLC cells releases SHC-binging protein 1 (SHCBP1) from SHC adaptor protein 1 (SHC1), which subsequently translocates into the nucleus and directly promotes the transactivating activity of β-catenin, consequently resulting in development of NSCLC cell stemness and malignant progression. Furthermore, SHCBP1 promotes β-catenin activity through enhancing the CBP/β-catenin interaction, and most interestingly, a candidate drug that blocks the CBP/β-catenin binding effectively abrogates the aforementioned biological effects of SHCBP1. Clinically, SHCBP1 level in NSCLC tumors was found to inversely correlate with patient survival. Together, our study establishes a novel convergence between EGFR and β-catenin pathways and highlights a potential significance of SHCBP1 as a prognostic biomarker and a therapeutic target.