AXL is an oncotarget in human colorectal cancer

Erika Martinelli, Giulia Martini, Claudia Cardone, Teresa Troiani, Giuseppina Liguori, Donata Vitagliano, Stefania Napolitano, Floriana Morgillo, Barbara Rinaldi, Rosa Marina Melillo, Federica Liotti, Anna Nappi, Roberto Bianco, Liberato Berrino, Loreta Pia Ciuffreda, Davide Ciardiello, Vincenzo Iaffaioli, Gerardo Botti, Fiorella Ferraiolo, Fortunato Ciardiello

Research output: Contribution to journalArticlepeer-review

Abstract

AXL is a tyrosine kinase receptor activated by GAS6 and regulates cancer cell proliferation migration and angiogenesis. We studied AXL as new therapeutic target in colorectal cancer (CRC). Expression and activation of AXL and GAS6 were evaluated in a panel of human CRC cell lines. AXL gene silencing or pharmacologic inhibition with foretinib suppressed proliferation, migration and survival in CRC cells. In an orthotopic colon model of human HCT116 CRC cells overexpressing AXL, foretinib treatment caused significant inhibition of tumour growth and peritoneal metastatic spreading. AXL and GAS6 overexpression by immunohistochemistry (IHC) were found in 76,7% and 73.5%, respectively, of 223 human CRC specimens, correlating with less differentiated histological grading. GAS6 overexpression was associated with nodes involvement and tumour stage. AXL gene was found amplified by Fluorescence in situ hybridization (FISH) in 8/146 cases (5,4%) of CRC samples. Taken together, AXL inhibition could represent a novel therapeutic approach in CRC.

Original languageEnglish
Pages (from-to)23281-23296
Number of pages16
JournalOncotarget
Volume6
Issue number27
DOIs
Publication statusPublished - 2015

Keywords

  • AXL
  • Colorectal cancer
  • FISH
  • Foretinib
  • GAS6

ASJC Scopus subject areas

  • Oncology

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