The receptor tyrosine kinase AXL promotes migration and invasion in colorectal cancer
| Autor: | Adam W. Watson, Jonathan A. Leighton, Diana J. Uribe, Sourav Ghosh, Carla V. Rothlin, Jesse D. Martinez, Edward K. Mandell |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Receptor Protein-Tyrosine Kinases lcsh:Medicine Pathology and Laboratory Medicine Biochemistry Receptor tyrosine kinase Metastasis 0302 clinical medicine Cell Movement Basic Cancer Research Medicine and Health Sciences Small interfering RNAs lcsh:Science Immune Response Multidisciplinary biology Animal Models 3. Good health Cancer Cell Migration Nucleic acids Gene Expression Regulation Neoplastic Cell Motility Oncology Experimental Organism Systems 030220 oncology & carcinogenesis Colorectal Neoplasms TYRO3 Research Article Immunology Mouse Models Cell Migration C-Mer Tyrosine Kinase Research and Analysis Methods Transfection 03 medical and health sciences Model Organisms Signs and Symptoms Diagnostic Medicine Cell Line Tumor Proto-Oncogene Proteins medicine Genetics Gene silencing Humans Neoplasm Invasiveness Kinase activity Non-coding RNA Molecular Biology Techniques Molecular Biology Cell Proliferation Colorectal Cancer Inflammation Biology and life sciences c-Mer Tyrosine Kinase business.industry lcsh:R Carcinoma Cancer Cancers and Neoplasms Cell Biology MERTK medicine.disease Axl Receptor Tyrosine Kinase Gene regulation 030104 developmental biology biology.protein Cancer research RNA lcsh:Q Gene expression business Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 12, Iss 7, p e0179979 (2017) |
| ISSN: | 1932-6203 |
| Popis: | The receptor tyrosine kinases (RTKs) TYRO3, AXL and MERTK (TAM) have well-described oncogenic functions in a number of cancers. Notwithstanding, TAM RTKs are also potent and indispensable inhibitors of inflammation. The combined deletion of Axl and Mertk in mice enhances chronic inflammation and autoimmunity, including increased inflammation in the gut and colitis-associated cancer. On the other hand, deletion of Tyro3 increases the risk of allergic responses. Therefore, the indiscriminate inhibition of these TAM RTKs could result in undesirable immunological diseases. Here we show that AXL, but not MERTK or TYRO3 expression is enhanced in late stage colorectal cancer (CRC) and AXL expression associates with a cell migration gene signature. Silencing AXL or the inhibition of AXL kinase activity significantly inhibits tumor cell migration and invasion. These results indicate that the selective inhibition of AXL alone might confer sufficient therapeutic benefit in CRC, while preserving at least some of the beneficial, anti-inflammatory effects of MERTK and TYRO3 RTKs. |
| Databáze: | OpenAIRE |
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