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ZFIN ID: ZDB-PUB-131021-11
The receptor tyrosine kinase Axl regulates cell-cell adhesion and stemness in cutaneous squamous cell carcinoma
CichoD, M.A., Szentpetery, Z., Caley, M.P., Papadakis, E.S., Mackenzie, I.C., Brennan, C.H., and O'Toole, E.A.
Date: 2014
Source: Oncogene   33(32): 4185-92 (Journal)
Registered Authors: Brennan, Caroline
Keywords: none
MeSH Terms:
  • Animals
  • Carcinoma, Squamous Cell/metabolism*
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Survival
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hyaluronan Receptors/metabolism
  • Isoenzymes/metabolism
  • Mice
  • Neoplasm Transplantation
  • Neoplastic Stem Cells/cytology*
  • Proto-Oncogene Proteins/physiology*
  • Receptor Protein-Tyrosine Kinases/physiology*
  • Receptors, Transforming Growth Factor beta/metabolism
  • Retinal Dehydrogenase/metabolism
  • Signal Transduction
  • Skin Neoplasms/metabolism*
  • Wnt Proteins/metabolism
  • Zebrafish
PubMed: 24056961 Full text @ Oncogene
ABSTRACT

Axl is a receptor tyrosine kinase (RTK) upregulated in various tumors including cutaneous squamous cell carcinoma (SCC). Axl expression correlates with poor prognosis and induction of epithelial–mesenchymal transition (EMT), hence we hypothesized that Axl is involved in the disruption of cell–cell adhesion to allow invasion and chemotherapy resistance of the cancer stem cell population. Cutaneous SCC cell lines with stable knockdown of Axl were generated using retroviral vectors. Axl depletion altered expression of intercellular junction molecules increasing cell–cell adhesion with downregulation of Wnt and TGFβR signaling. Furthermore, Axl expression correlated with the expression of putative cancer stem cell markers, CD44 and ALDH1, increased resistance to chemotherapy drugs, enhanced sphere formation ability and expression of EMT features by cancer stem cells. Axl depletion resulted in loss of tumor formation in an in vivo zebrafish xenograft model. In conclusion, these data suggest that abrogation of Axl results in loss of cancer stem cell properties indicating a role for Axl as a therapeutic target in chemotherapy-resistant cancer.

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