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

<div><p>The receptor tyrosine kinases (RTKs) <i>TYRO3</i>, <i>AXL</i> and <i>MERTK</i> (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 <i>Axl</i> and <i>Mertk</i> in mice enhances chronic inflammation and autoimmunity, including increased inflammation in the gut and colitis-associated cancer. On the other hand, deletion of <i>Tyro3</i> increases the risk of allergic responses. Therefore, the indiscriminate inhibition of these TAM RTKs could result in undesirable immunological diseases. Here we show that <i>AXL</i>, but not <i>MERTK</i> or <i>TYRO3</i> expression is enhanced in late stage colorectal cancer (CRC) and <i>AXL</i> expression associates with a cell migration gene signature. Silencing <i>AXL</i> 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.</p>