Tripartite Motif Protein 6 Promotes Colorectal Cancer Cell Migration and Metastasis via SOCS2-STAT3 Signaling.

Hongjian Zhao,Junjun Huang,Baoru Li,Xinran Chen,Mingqing Zhou,Ming Chen

doi:10.3389/fonc.2021.695525

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide, with most mortalities being caused by metastases. However, the underlying molecular mechanism of CRC metastases remains largely unknown. Emerging evidence has shown the role of the tripartite motif family, especially tripartite motif protein 6 (TRIM6), in carcinogenesis. In this study, we used CRC cell lines with TRIM6 knockdown and overexpression to investigate the function of TRIM6 in CRC metastasis. We found that TRIM6 promotes CRC cell migration and invasion both in vitro and in vivo. TRIM6 knockdown slows down the migration and invasion processes, whereas TRIM6 overexpression accelerates CRC cell migration and invasion. TRIM6 is potentially the upstream regulatory factor for signal transducer and activator of transcription 3 (STAT3) via the suppressor of cytokine signaling 2 (SOCS2). A total of 70 samples from patients with CRC further confirmed that TRIM6 expression level is positively correlated with STAT3 phosphorylation and negatively correlated with SOCS2 expression. Therefore, TRIM6 could be a potential therapeutic target for CRC metastasis.

Highlights

Colorectal cancer (CRC) accounts for 9% of all cancers worldwide, being the second most common cancer in women and the third most common cancer in men [1, 2]
To investigate the function of tripartite motif protein 6 (TRIM6) in CRC cell migration, we knocked down the TRIM6 expression in HCT116 cells using lentivirus-mediated Short hairpin RNA (shRNA)
These results indicate that TRIM6 knockdown potentially inhibits CRC cell migration and invasion

Summary

Introduction

Colorectal cancer (CRC) accounts for 9% of all cancers worldwide, being the second most common cancer in women and the third most common cancer in men [1, 2]. CRC metastasis is a highly integrated process, involving processes such as cancer cell migration, adhesion, and invasion [5]. These processes require precise molecular and cellular regulation, including cell adhesion molecules [6], cell–matrix interactions [7], and epithelial–mesenchymal transition (EMT), among others [8]. Multiple signaling pathways, including the transforming growth factor beta (TGF-b) [9], Wnt [10], Notch [11], signal transducer and activator of transcription 3 (STAT3) [12], and PI3K/ AKT [13], have been linked to cancer metastasis. The underlying mechanisms of CRC metastasis remain largely unknown

Methods

Results

Conclusion