Downregulation of STK4 promotes colon cancer invasion/migration through blocking β‐catenin degradation. Issue 10 (25th August 2020)

• Record Type: Journal Article
• Authors: Lin, Cheng‐Han; Hsu, Tai‐I; Chiou, Pei‐Yu; Hsiao, Michael; Wang, Wen‐Ching; Chen, Yu‐Chia; Lin, Jen‐Tai; Wang, Jaw‐Yuan; Lin, Peng‐Chan; Lin, Forn‐Chia; Tseng, Yu‐Kai; Cheng, Hui‐Chuan; Chen, Chi‐Long; Lu, Pei‐Jung
• Is Part Of: Molecular oncology. Volume 14:Issue 10(2020)
• Page Start: 2574
• Page End: 2588
• Publication Date: 2020-08-25
• Subjects: colon cancers -- STK4 -- β‐catenin; Cancer -- Molecular aspects -- Periodicals; 616.994005
• DOI: 10.1002/1878-0261.12771
• Languages: English
• ISSNs: 1574-7891

Abstract

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. Abstract : Here, we found that STK4 was significantly downregulated in colon cancer and was associated with distal metastasis and poor survival. 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.