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 Berrin; Loreta Pia Ciuffreda; Davide Ciardiello; Vincenzo Iaffaioli; Gerardo Botti; Fiorella Ferraiolo; Fortunato Ciardiello

doi:10.18632/oncotarget.3962

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Research Papers: Pathology:

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 Berrin, Loreta Pia Ciuffreda, Davide Ciardiello, Vincenzo Iaffaioli, Gerardo Botti, Fiorella Ferraiolo and Fortunato Ciardiello

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Oncotarget. 2015; 6:23281-23296. https://doi.org/10.18632/oncotarget.3962

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Abstract

Erika Martinelli1, Giulia Martini1,*, Claudia Cardone1,*, Teresa Troiani1, Giuseppina Liguori2, Donata Vitagliano1, Stefania Napolitano1, Floriana Morgillo1, Barbara Rinaldi3, Rosa Marina Melillo4, Federica Liotti4, Anna Nappi5, Roberto Bianco6, Liberato Berrino3, Loreta Pia Ciuffreda3, Davide Ciardiello1, Vincenzo Iaffaioli5, Gerardo Botti2, Fiorella Ferraiolo3 and Fortunato Ciardiello1

1 Oncologia Medica, Dipartimento di Internistica Clinica e Sperimentale “F. Magrassi “, Seconda Università degli Studi di Napoli, Via S. Pansini, Napoli, Italia

2 Dipartimento di Patologia Diagnostica e di Laboratorio, Istituto Nazionale Tumori- IRCCS “Fondazione G. Pascale”, Via M Semmola, Napoli, Italia

3 Sezione di Farmacologia, Dipartimento di Medicina Sperimentale, Seconda Università degli Studi di Napoli, Via L. De Crecchio, Napoli, Italia

4 Dipartimento di Medicina Molecolare e Biotecnologie Mediche/Istituto di Endocrinologia ed Oncologia Sperimentale del CNR ”G. Salvatore”, via Pansini, Napoli, Italia

5 Oncologia Medica A, Istituto Nazionale Tumori- IRCCS “Fondazione G. Pascale”, Via M Semmola, Napoli, Italia

6 Oncologia Medica, Dipartimento di Medicina Clinica e Chirurgica, Università Federico II di Napoli, Italia

* These authors have contributed equally in the manuscript

Correspondence to:

Erika Martinelli, email:

Keywords: AXL, GAS6, colorectal cancer, foretinib, FISH

Received: March 03, 2015 Accepted: April 11, 2015 Published: April 29, 2015

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.

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Research Papers: Pathology:

AXL is an oncotarget in human colorectal cancer

Abstract