TY - JOUR
T1 - Axl receptor in cancer metastasis and drug resistance
T2 - when normal functions go askew
AU - Auyez, Almira
AU - Sayan, A. Emre
AU - Kriajevska, Marina
AU - Tulchinsky, Eugene
N1 - Funding Information:
The research in E.T. and M.K. labs is supported by Nazarbayev University Faculty Development Research Grants (240919FD3909 to ET and 080420FD1908 to M.K.). The APC was funded by the University of Southampton.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - 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.
AB - 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.
KW - AXL
KW - Drug resistance
KW - Epithelial‐mesenchymal plasticity
KW - Metastasis
KW - TAM receptors
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U2 - 10.3390/cancers13194864
DO - 10.3390/cancers13194864
M3 - Review article
AN - SCOPUS:85115882391
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 19
M1 - 4864
ER -
