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 language | English (US) |
|---|---|
| Article number | e0179979 |
| Journal | PLoS One |
| Volume | 12 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1 2017 |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - The receptor tyrosine kinase AXL promotes migration and invasion in colorectal cancer
AU - Uribe, Diana J.
AU - Mandell, Edward K.
AU - Watson, Adam
AU - Martinez, Jesse D
AU - Leighton, Jonathan A.
AU - Ghosh, Sourav
AU - Rothlin, Carla V.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85024848067&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85024848067&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0179979
DO - 10.1371/journal.pone.0179979
M3 - Article
C2 - 28727830
AN - SCOPUS:85024848067
VL - 12
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 7
M1 - e0179979
ER -