E3 ubiquitin ligase HECW1 promotes the metastasis of non-small cell lung cancer cells through mediating the ubiquitination of Smad4.

E3 ubiquitin ligase HECW1 promotes the metastasis of non-small cell lung cancer cells through mediating the ubiquitination of Smad4.
Biochem Cell Biol. 2021 Feb 02;:
Authors: Lu C, Ning G, Si P, Zhang C, Liu W, Ge W, Cui K, Zhang R, Ge S
Abstract
Lung cancer is the leading cause of cancer-related death globally. Ubiquitin modification plays a crucial role in regulation of gene expression, and is closely related to cancer pathogenesis. The aim of our study is to demystify the role and action mechanism of HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1 (HECW1) in non-small cell lung cancer (NSCLC). Here, we demonstrated that HECW1 expression was notably increased in NSCLC cell lines and tissues. Increasing of HECW1 markedly enhanced, whereas decreasing of HECW1 notably inhibited the proliferation of NSCLC cells. Moreover, the expression levels of HECW1 positively correlated with the ability of NSCLC cells migration and invasion. Increasing of HECW1 or silencing of HECW1 only affected the SMAD family member 4 (Smad4) protein level, but not have no effect on its mRNA level. Furthermore, after treatment with MG-132, the relative protein level of Smad4 significantly increased in NSCLC cells. HECW1 promoted the proliferation, migration and invasion of NSCLC cells by inducing the ubiquitination and degradation of Smad4. Our data provided a novel target for NSCLC treatment.
PMID: 33529121 [PubMed - as supplied by publi...

Source: Biochemistry and Cell Biology - February 2, 2021 Category: Biochemistry Authors: Lu C, Ning G, Si P, Zhang C, Liu W, Ge W, Cui K, Zhang R, Ge S Tags: Biochem Cell Biol Source Type: research