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

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.

Upregulation of centromere protein�M promotes tumorigenesis: A potential predictive target for cancer in humans

“…The protein interaction network identified nine key genes [RAD51 (29), KIF4A (30), RACGAP1 (31), SPAG5 (32), HMMr (33), cdc25c (34), cKS2 (35), SHcBP1 (36) and ERCC6L (37)] that interacted strongly with CENPM mRNA. Subsequently, the functions of these nine genes (38)(39)(40)(41)(42)(43)(44)(45)(46) were profiled in various types of cancer and it was identified that all of them have been reported to accelerate the progression of cancer, including BC and hepatocellular carcinoma (29)(30)(31)(32)(33)(34)(35)(36)(37). RT-qPCR demonstrated that the expression levels of five of the nine genes, ERCC6L, CKS2, KIF4A, SPAG5 and CDC25C, were increased in MCF7 cells with elevated CENPM expression, implying that cenPM may promote tumor progression by controlling the expression of these five genes.…”

PRMT5 promotes epithelial‐mesenchymal transition via EGFR‐β‐catenin axis in pancreatic cancer cells

“…21 More recently, PRMT5 was demonstrated that lead to FBW7 expression to promote tumorigenesis in pancreatic cancer. 14 ling, 24 and EGF-induced nuclear translocation of SHCBP1 directly increased acetylation of β-catenin to enhanced NSCLC cellular stemness, 25 which is suggested that EGFR signalling can drive β-catenin activation via various routes. In this study, we provide a novel F I G U R E 2 PRMT5 promotes cell proliferation in pancreatic cancer cells and tumorigenesis.…”

MTNR1B loss promotes chordoma recurrence by abrogating melatonin‐mediated β‐catenin signaling repression

“…IHC assays in chordoma tissues were performed and quantified according to our previous report . The degree of immunostaining of the indicated proteins was evaluated and scored by two independent observers as previously described, scoring both the proportions of positively stained tumor cells and their staining intensities.…”