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Oncotarget. 2015 Sep 15;6(27):23281-96.

AXL is an oncotarget in human colorectal cancer.

Author information

1
Oncologia Medica, Dipartimento di Internistica Clinica e Sperimentale "F. Magrassi ", Seconda Università degli Studi di Napoli, Napoli, Italia.
2
Dipartimento di Patologia Diagnostica e di Laboratorio, Istituto Nazionale Tumori- IRCCS "Fondazione G. Pascale", Napoli, Italia.
3
Sezione di Farmacologia, Dipartimento di Medicina Sperimentale, Seconda Università degli Studi di Napoli, Napoli, Italia.
4
Dipartimento di Medicina Molecolare e Biotecnologie Mediche/Istituto di Endocrinologia ed Oncologia Sperimentale del CNR "G. Salvatore", Napoli, Italia.
5
Oncologia Medica A, Istituto Nazionale Tumori- IRCCS "Fondazione G. Pascale", Napoli, Italia.
6
Oncologia Medica, Dipartimento di Medicina Clinica e Chirurgica, Università Federico II di Napoli, Napoli, Italia.

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.

KEYWORDS:

AXL; FISH; GAS6; Pathology Section; colorectal cancer; foretinib

PMID:
25966280
PMCID:
PMC4695118
DOI:
10.18632/oncotarget.3962
[Indexed for MEDLINE]
Free PMC Article

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