Journal article
Serine Threonine Kinase 17A Maintains the Epithelial State in Colorectal Cancer Cells
Molecular cancer research, Vol.17(4), pp.882-894
04/01/2019
DOI: 10.1158/1541-7786.MCR-18-0990
PMCID: PMC6941354
PMID: 30655319
Abstract
Serine threonine kinase 17A (STK17A) is a ubiquitously expressed kinase originally identified as a regulator of apoptosis; however, whether it functionally contributes to colorectal cancer has not been established. Here, we have analyzed STK17A in colorectal cancer and demonstrated decreased expression of STK17A in primary tumors, which is further reduced in metastatic lesions, indicating a potential role in regulating the metastatic cascade. Interestingly, changes in STK17A expression did not modify proliferation, apoptosis, or sensitivity of colorectal cancer cell lines to treatment with the chemotherapeutic 5-fluorouracil. Instead,
knockdown induced a robust mesenchymal phenotype consistent with the epithelial-mesenchymal transition, including spindle-like cell morphology, decreased expression of adherens junction proteins, and increased migration and invasion. Additionally, overexpression of
decreased cell size and induced widespread membrane blebbing, a phenotype often associated with activation of cell contractility. Indeed, STK17A-overexpressing cells displayed heightened phosphorylation of myosin light chain in a manner dependent on STK17A catalytic activity. Finally, patient-derived tumor organoid cultures were used to more accurately determine STK17A's effect in primary human tumor cells. Loss of STK17A induced morphologic changes, decreased E-cadherin, increased invasion, and augmented organoid attachment on 2D substrates, all together suggesting a more metastatic phenotype. Collectively, these data indicate a novel role for STK17A in the regulation of epithelial phenotypes and indicate its functional contribution to colorectal cancer invasion and metastasis. IMPLICATIONS: Loss of serine threonine kinase 17A occurs in colorectal cancer metastasis, induces mesenchymal morphologies, and contributes to tumor cell invasion and migration in colorectal cancer.
Details
- Title: Subtitle
- Serine Threonine Kinase 17A Maintains the Epithelial State in Colorectal Cancer Cells
- Creators
- Sarah P Short - Vanderbilt University Medical CenterJoshua J Thompson - Vanderbilt University Medical CenterAnthony J Bilotta - Vanderbilt University Medical CenterXi Chen - Sylvester Comprehensive Cancer CenterFrank L Revetta - Vanderbilt University Medical CenterM Kay Washington - Vanderbilt University Medical CenterChristopher S Williams - Vanderbilt University Medical Center
- Resource Type
- Journal article
- Publication Details
- Molecular cancer research, Vol.17(4), pp.882-894
- DOI
- 10.1158/1541-7786.MCR-18-0990
- PMID
- 30655319
- PMCID
- PMC6941354
- NLM abbreviation
- Mol Cancer Res
- ISSN
- 1541-7786
- eISSN
- 1557-3125
- Grant note
- P50 CA236733 / NCI NIH HHS UL1 TR002243 / NCATS NIH HHS F30 DK111107 / NIDDK NIH HHS R01 DK099204 / NIDDK NIH HHS P30 DK058404 / NIDDK NIH HHS F32 DK108492 / NIDDK NIH HHS K08 DK080221 / NIDDK NIH HHS I01 BX001426 / BLRD VA
- Language
- English
- Date published
- 04/01/2019
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984420842702771
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