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


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 ?-catenin and directly phosphorylated ?-catenin resulting in its degradation via the ubiquitin-mediated pathway. This may suggest that STK4 knockdown causes ?-catenin phosphorylation failure and subsequently ?-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 ?-catenin-mediated colon cancer prognosis.

SUBMITTER: Lin CH 

PROVIDER: S-EPMC7530774 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Lin Cheng-Han CH   Hsu Tai-I TI   Chiou Pei-Yu PY   Hsiao Michael M   Wang Wen-Ching WC   Chen Yu-Chia YC   Lin Jen-Tai JT   Wang Jaw-Yuan JY   Lin Peng-Chan PC   Lin Forn-Chia FC   Tseng Yu-Kai YK   Cheng Hui-Chuan HC   Chen Chi-Long CL   Lu Pei-Jung PJ  

Molecular oncology 20200825 10


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 understu  ...[more]

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