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PLoS One. 2017 Jul 20;12(7):e0179979. doi: 10.1371/journal.pone.0179979. eCollection 2017.

The receptor tyrosine kinase AXL promotes migration and invasion in colorectal cancer.

Author information

1
Arizona Cancer Center, University of Arizona, Tucson, Arizona, United States of America.
2
Division of Gastroenterology, Mayo Clinic Arizona, Scottsdale, Arizona, United States of America.
3
Department of Neurology, Pharmacology and Yale Cancer Center, School of Medicine, Yale University, New Haven, Connecticut, United States of America.
4
Department of Immunobiology, Pharmacology and Yale Cancer Center, School of Medicine, Yale University, New Haven, Connecticut, United States of America.

Abstract

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.

PMID:
28727830
PMCID:
PMC5519024
DOI:
10.1371/journal.pone.0179979
[Indexed for MEDLINE]
Free PMC Article

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