Apoptotic Bodies Elicit Gas6-Mediated Migration of AXL-Expressing Tumor Cells

作者：Zweemer Annelien J M; French Cory B; Mesfin Joshua; Gordonov Simon; Meyer Aaron S^*; Lauffenburger Douglas A^*

来源：Molecular Cancer Research, 2017, 15(12): 1656-1666.

DOI：10.1158/1541-7786.MCR-17-0012

Metastases are a major cause of cancer mortality. AXL, a receptor tyrosine kinase aberrantly expressed in many tumors, is a potent oncogenic driver of metastatic cell motility and has been identified as broadly relevant in cancer drug resistance. Despite its frequent association with changes in cancer phenotypes, the precise mechanism leading to AXL activation is incompletely understood. In addition to its ligand growth arrest specific-6 (Gas6), activation of AXL requires the lipid moiety phosphatidylserine (PS). Phosphatidylserine is only available to mediate AXL activation when it is externalized on cell membranes, an event that occurs during certain physiologic processes such as apoptosis. Here, it is reported that exposure of cancer cells to phosphatidylserine-containing vesicles, including synthetic liposomes and apoptotic bodies,contributes to enhanced migration of tumor cells via a PSGas6-AXL signaling axis. These findings suggest that anticancer treatments that induce fractional cell killing enhance the motility of surviving cells in AXL-expressing tumors, which may explain the widespread role of AXL in limiting therapeutic efficacy.

• 出版日期2017-12
• 单位MIT