The receptor tyrosine kinase AXL promotes migration and invasion in colorectal cancer
AuthorUribe, Diana J.
Mandell, Edward K.
Martinez, Jesse D.
Leighton, Jonathan A.
Rothlin, Carla V.
AffiliationUniv Arizona, Arizona Canc Ctr
MetadataShow full item record
PublisherPUBLIC LIBRARY SCIENCE
CitationThe receptor tyrosine kinase AXL promotes migration and invasion in colorectal cancer 2017, 12 (7):e0179979 PLOS ONE
Rights© 2017 Uribe et al. This is an open access article distributed under the terms of the Creative Commons Attribution License.
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AbstractThe 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.
NoteOpen access journal.
VersionFinal published version
SponsorsNational Institutes of Health [R01 A1089824, R01 CA212376, R01 CA149258-S]; Crohn's and Colitis Foundation