Rgl2 drives the metastatic progression of colorectal cancer via preventing the protein degradation of β-catenin and kras

Meng Shun Sun, Lan Ting Yuan, Chia Hao Kuei, Hui Yu Lin, Yen Lin Chen, Hui Wen Chiu, Yuan Feng Lin

Research output: Contribution to journalArticlepeer-review

Abstract

Colorectal cancer (CRC) is one of the most common cancers and results in high mortality worldwide, owing to cancer progression, i.e., metastasis. However, the molecular mechanism underlying the metastatic evolution of CRC remains largely unknown. Here, we find that the upregulation of Ral Guanine Nucleotide Dissociation Stimulator Like 2 (RGL2) is commonly detected in primary tumors compared normal tissues and is significantly associated with a poorer prognosis in CRC patients. Moreover, RGL2 expression appeared to positively correlate with the metastatic potentials of CRC cells. Whereas RGL2 knockdown dramatically suppresses the metastatic potentials of CRC cells in vitro and in vivo, RGL2 overexpression in the poorly metastatic CRC cells and reconstitution in the RGL2-silenced CRC cells enhanced and rescued the cellular metastatic ability, respectively. Computational simulation using Gene Set Enrichment Analysis program and cell-based assays demonstrated that RGL2 expression causally associated with the activity of Wnt/β-catenin signaling axis and Kirsten ras (KRAS)S, as well as the progression of epithelial-mesenchymal transition (EMT) in the detected CRC cells. Importantly, RGL2 upregulation was capable of preventing the protein degradation of β-catenin and KRAS in CRC cells. These findings suggest that RGL2 acts as a driver to promote the metastatic progression of CRC and also serves as a poor prognostic biomarker in CRC patients.

Original languageEnglish
Article number1763
JournalCancers
Volume13
Issue number8
DOIs
Publication statusPublished - Apr 2 2021

Keywords

  • Colorectal cancer
  • KRAS
  • Metastasis
  • RGL2
  • Wnt/β-catenin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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