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

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 ?-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 ?-catenin, consequently resulting in development of NSCLC cell stemness and malignant progression. Furthermore, SHCBP1 promotes ?-catenin activity through enhancing the CBP/?-catenin interaction, and most interestingly, a candidate drug that blocks the CBP/?-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 ?-catenin pathways and highlights a potential significance of SHCBP1 as a prognostic biomarker and a therapeutic target.
Mesh Terms:
Active Transport, Cell Nucleus, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Cell Nucleus, Epidermal Growth Factor, Humans, Lung Neoplasms, Neoplasm Proteins, Shc Signaling Adaptor Proteins, beta Catenin
Oncogene
Date: Jan. 01, 2019
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