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AXL-Driven EMT State as a Targetable Conduit in Cancer

Jane Antony1,2,3, Ruby Yun-Ju Huang4,5,6

  • 1Cancer Science Institute of Singapore, National University of Singapore, Singapore.

Cancer Research
|July 2, 2017
PubMed

Insights

The receptor tyrosine kinase AXL drives cancer progression and drug resistance by promoting epithelial-mesenchymal transition (EMT). Inhibiting AXL may reverse EMT and resensitize tumors to therapy, necessitating patient stratification for targeted treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The receptor tyrosine kinase (RTK) AXL is implicated in epithelial-mesenchymal transition (EMT), enhancing cancer cell survival, invasion, and metastasis.
  • AXL signaling confers an aggressive phenotype and drug resistance by directly influencing the mesenchymal state.
  • Recent findings reveal EMT-induced rewiring of kinase signaling nodes, facilitating AXL cross-talk and sustained signaling through ERK and PI3K pathways.

Purpose of the Study:

  • To elucidate the molecular mechanisms regulating the interplay between the kinome and EMT.
  • To highlight the reciprocal control between AXL signaling and the EMT state in oncogenesis.
  • To review the therapeutic potential of AXL inhibition for developing novel cancer treatments.

Main Methods:

  • Literature review of studies on AXL, EMT, and cancer signaling pathways.
  • Analysis of molecular mechanisms underlying AXL-EMT crosstalk.
  • Evaluation of therapeutic strategies targeting AXL.

Main Results:

  • AXL plays a crucial role in EMT-mediated oncogenesis, promoting aggressive cancer phenotypes.
  • AXL signaling contributes to resistance against various cancer therapies.
  • AXL inhibition has demonstrated potential in reversing EMT and resensitizing cancer cells to treatments.

Conclusions:

  • Understanding the AXL-EMT axis is critical for developing targeted cancer therapies.
  • AXL inhibition represents a promising therapeutic strategy for overcoming drug resistance in various cancers.
  • Patient stratification based on AXL dependence is essential for optimizing treatment outcomes.

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