Downregulation of STK4 promotes colon cancer invasion/migration through blocking β-catenin degradation

Cheng Han Lin, Tai I. Hsu, Pei Yu Chiou, Michael Hsiao, Wen Ching Wang, Yu Chia Chen, Jen Tai Lin, Jaw Yuan Wang, Peng Chan Lin, Forn Chia Lin, Yu Kai Tseng, Hui Chuan Cheng, Chi Long Chen, Pei Jung Lu

Research output: Contribution to journalArticlepeer-review

Abstract

Mammalian STE20-like kinase 1 (MST1/STK4/KRS2) encodes a serine/threonine kinase that is the mammalian homolog of Drosophila Hippo. STK4 plays an important role in controlling cell growth, apoptosis, and organ size. STK4 has been studied in many cancers with previous studies indicating an involvement in colon cancer lymph node metastasis and highlighting its potential as a diagnostic marker for colon cancer. However, the role of STK4 defect in promoting colon cancer progression is still understudied. Here, we found that STK4 was significantly downregulated in colon cancer and was associated with distal metastasis and poor survival. Furthermore, STK4 knockdown enhanced sphere formation and metastasis in vitro and promoted tumor development in vivo. We found that STK4 colocalized with β-catenin and directly phosphorylated β-catenin resulting in its degradation via the ubiquitin-mediated pathway. This may suggest that STK4 knockdown causes β-catenin phosphorylation failure and subsequently β-catenin accumulation, consequently leading to anchorage-independent growth and metastasis in colon cancer. Our results support that STK4 may act as a potential candidate for the assessment of β-catenin-mediated colon cancer prognosis.

Original languageEnglish
Pages (from-to)2574-2588
Number of pages15
JournalMolecular Oncology
Volume14
Issue number10
DOIs
Publication statusPublished - 2020 Oct 1

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Oncology
  • Cancer Research

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