Human cutaneous melanomas lacking MITF and melanocyte differentiation antigens express a functional Axl receptor kinase

Marialuisa Sensi, Mara Catani, Giancarlo Castellano, Gabriella Nicolini, Federica Alciato, Gabrina Tragni, Giuseppina De Santis, Ilaria Bersani, Giancarlo Avanzi, Antonella Tomassetti, Silvana Canevari, Andrea Anichini

Research output: Contribution to journalArticlepeer-review

Abstract

Axl, a member of the TAM (Tyro3, Axl, Mer) family of receptor tyrosine kinases, displays an increasingly important role in carcinogenesis. Analysis of 58 cutaneous melanoma lines indicated that Axl was expressed in 38% of them, with significant overrepresentation in NRAS-compared with BRAF-mutated tumors. Axl activation could be induced by autocrine production of its ligand, Gas6, in a significant fraction of Axl-positive tumors. Pearson's correlation analysis on expression data from five data sets of melanoma lines identified several transcripts correlating positively or negatively with Axl. By functionally grouping genes, those inversely correlated were involved in melanocyte development and pigmentation, whereas those positively correlated were involved in motility, invasion, and microenvironment interactions. Accordingly, Axl-positive melanomas did not express microphthalmia transcription factor (MITF) and melanocyte differentiation antigens (MDAs) such as MART-1 and gp100 and possessed a greater in vitro invasive potential compared with Axl-negative ones. Motility, invasivity, and ability to heal a wound or to migrate across an endothelial barrier were inhibited in vitro by Axl knockdown. Pharmacological inhibition of Axl using the selective inhibitor R428 had comparable effects in reducing migration and invasion. These results suggest that targeted inhibition of Axl signaling in the subset of melanomas lacking MITF and MDAs may represent a novel therapeutic strategy.

Original languageEnglish
Pages (from-to)2448-2457
Number of pages10
JournalJournal of Investigative Dermatology
Volume131
Issue number12
DOIs
Publication statusPublished - Dec 2011

ASJC Scopus subject areas

  • Dermatology
  • Biochemistry
  • Cell Biology
  • Molecular Biology

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