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Review

AXL-Driven EMT State as a Targetable Conduit in Cancer

Jane Antony and Ruby Yun-Ju Huang
Jane Antony
Cancer Science Institute of Singapore, National University of Singapore, Singapore.NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
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Ruby Yun-Ju Huang
Cancer Science Institute of Singapore, National University of Singapore, Singapore.Department of Obstetrics and Gynecology, National University Health System, Singapore.Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
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  • For correspondence: ruby_yj_huang@nuhs.edu.sg
DOI: 10.1158/0008-5472.CAN-17-0392
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Abstract

The receptor tyrosine kinase (RTK) AXL has been intrinsically linked to epithelial–mesenchymal transition (EMT) and promoting cell survival, anoikis resistance, invasion, and metastasis in several cancers. AXL signaling has been shown to directly affect the mesenchymal state and confer it with aggressive phenotype and drug resistance. Recently, the EMT gradient has also been shown to rewire the kinase signaling nodes that facilitate AXL–RTK cross-talk, protracted signaling, converging on ERK, and PI3K axes. The molecular mechanisms underplaying the regulation between the kinome and EMT require further elucidation to define targetable conduits. Therapeutically, as AXL inhibition has shown EMT reversal and resensitization to other tyrosine kinase inhibitors, mitotic inhibitors, and platinum-based therapy, there is a need to stratify patients based on AXL dependence. This review elucidates the role of AXL in EMT-mediated oncogenesis and highlights the reciprocal control between AXL signaling and the EMT state. In addition, we review the potential in inhibiting AXL for the development of different therapeutic strategies and inhibitors. Cancer Res; 77(14); 1–8. ©2017 AACR.

  • Received February 13, 2017.
  • Revision received April 19, 2017.
  • Accepted May 22, 2017.
  • ©2017 American Association for Cancer Research.

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Published OnlineFirst June 30, 2017
doi: 10.1158/0008-5472.CAN-17-0392

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AXL-Driven EMT State as a Targetable Conduit in Cancer
Jane Antony and Ruby Yun-Ju Huang
Cancer Res June 30 2017 DOI: 10.1158/0008-5472.CAN-17-0392

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AXL-Driven EMT State as a Targetable Conduit in Cancer
Jane Antony and Ruby Yun-Ju Huang
Cancer Res June 30 2017 DOI: 10.1158/0008-5472.CAN-17-0392
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Cancer Research Online ISSN: 1538-7445
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