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Oncogene. 2019 Jan;38(5):747-764. doi: 10.1038/s41388-018-0473-z. Epub 2018 Sep 3.

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

Liu L1,2, Yang Y3,4, Liu S1,2, Tao T1,2, Cai J1,2, Wu J1,2, Guan H5, Zhu X1,6, He Z1,7, Li J1,8, Song E9, Zeng M10, Li M11,12.

Author information

1
Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, Guangdong, China.
2
Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
3
Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, Guangdong, China. yangyi23@mail.sysu.edu.cn.
4
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China. yangyi23@mail.sysu.edu.cn.
5
Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
6
Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Guangzhou, Guangdong, China.
7
School of Public-Health, Sun Yat-Sen University, Guangzhou, Guangdong, China.
8
Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China.
9
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
10
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
11
Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, Guangdong, China. limf@mail.sysu.edu.cn.
12
Department of Microbiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong, China. limf@mail.sysu.edu.cn.

Abstract

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.

PMID:
30177836
PMCID:
PMC6355651
DOI:
10.1038/s41388-018-0473-z
[Indexed for MEDLINE]
Free PMC Article

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