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

Diana J. Uribe, Edward K. Mandell, Adam Watson, Jesse D. Martinez, Jonathan A Leighton, Sourav Ghosh, Carla V. Rothlin

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere0179979
JournalPLoS One
Volume12
Issue number7
DOIs
StatePublished - Jul 1 2017

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Receptor Protein-Tyrosine Kinases
colorectal neoplasms
tyrosine
Colorectal Neoplasms
phosphotransferases (kinases)
receptors
Inflammation
inflammation
Cell Movement
cell movement
immunologic diseases
Neoplasms
Immune System Diseases
Colitis
Autoimmunity
autoimmunity
neoplasms
cell invasion
colitis
Tumors

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Uribe, D. J., Mandell, E. K., Watson, A., Martinez, J. D., Leighton, J. A., Ghosh, S., & Rothlin, C. V. (2017). The receptor tyrosine kinase AXL promotes migration and invasion in colorectal cancer. PLoS One, 12(7), [e0179979]. https://doi.org/10.1371/journal.pone.0179979

The receptor tyrosine kinase AXL promotes migration and invasion in colorectal cancer. / Uribe, Diana J.; Mandell, Edward K.; Watson, Adam; Martinez, Jesse D.; Leighton, Jonathan A; Ghosh, Sourav; Rothlin, Carla V.

In: PLoS One, Vol. 12, No. 7, e0179979, 01.07.2017.

Research output: Contribution to journalArticle

Uribe, DJ, Mandell, EK, Watson, A, Martinez, JD, Leighton, JA, Ghosh, S & Rothlin, CV 2017, 'The receptor tyrosine kinase AXL promotes migration and invasion in colorectal cancer', PLoS One, vol. 12, no. 7, e0179979. https://doi.org/10.1371/journal.pone.0179979
Uribe, Diana J. ; Mandell, Edward K. ; Watson, Adam ; Martinez, Jesse D. ; Leighton, Jonathan A ; Ghosh, Sourav ; Rothlin, Carla V. / The receptor tyrosine kinase AXL promotes migration and invasion in colorectal cancer. In: PLoS One. 2017 ; Vol. 12, No. 7.
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