Figure 1.

Cancer cell intrinsic implication of AXL in the metastatic cascade. In cancer cells, AXL expression can be enhanced by EMT, hypoxia and TGF-β leading to metastatic progression. Indeed, various cellular pathways downstream of AXL confer advantages to cancer cells such as survival, proliferation, cell invasion and migration, EMT and therapy resistance. Consequently, AXL is required throughout the metastatic cascade for local invasion, intravasation, extravasation and metastatic growth at distant sites. In the bones, AXL expression on disseminated cells increases the survival and dormancy of cancer cells by stimulating the expression of TGF-β2 and TGF-βRs. In the lungs, AXL expression in cancer cells is linked to THSB2 secretion, which activates the fibroblasts in the metastatic niche to promote metastatic growth.