Axl receptor in cancer metastasis and drug resistance: when normal functions go askew

Almira Auyez, A. Emre Sayan, Marina Kriajevska, Eugene Tulchinsky

Research output: Contribution to journalReview articlepeer-review

15 Citations (Scopus)


The TAM proteins TYRO3, AXL, and MER are receptor tyrosine kinases implicated in the clearance of apoptotic debris and negative regulation of innate immune responses. AXL contributes to immunosuppression by terminating the Toll‐like receptor signaling in dendritic cells, and suppress-ing natural killer cell activity. In recent years, AXL has been intensively studied in the context of can-cer. Both molecules, the receptor, and its ligand GAS6, are commonly expressed in cancer cells, as well as stromal and infiltrating immune cells. In cancer cells, the activation of AXL signaling stimulates cell survival and increases migratory and invasive potential. In cells of the tumour microenvironment, AXL pathway potentiates immune evasion. AXL has been broadly implicated in the epithelial‐mesen-chymal plasticity of cancer cells, a key factor in drug resistance and metastasis. Several antibody‐based and small molecule AXL inhibitors have been developed and used in preclinical studies. AXL inhibition in various mouse cancer models reduced metastatic spread and improved the survival of the an-imals. AXL inhibitors are currently being tested in several clinical trials as monotherapy or in combi-nation with other drugs. Here, we give a brief overview of AXL structure and regulation and discuss the normal physiological functions of TAM receptors, focusing on AXL. We present a theory of how epithelial cancers exploit AXL signaling to resist cytotoxic insults, in order to disseminate and relapse.

Original languageEnglish
Article number4864
Issue number19
Publication statusPublished - Oct 1 2021


  • AXL
  • Drug resistance
  • Epithelial‐mesenchymal plasticity
  • Metastasis
  • TAM receptors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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