title: AXL is an oncotarget in human colorectal cancer.
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.
authors.affiliation: Oncologia Medica, Dipartimento di Internistica Clinica e Sperimentale "F. Magrassi ", Seconda Università degli Studi di Napoli, Napoli, Italia.
authors.forename: Erika
authors.initials: E
authors.lastname: Martinelli
authors.affiliation: Oncologia Medica, Dipartimento di Internistica Clinica e Sperimentale "F. Magrassi ", Seconda Università degli Studi di Napoli, Napoli, Italia.
authors.forename: Giulia
authors.initials: G
authors.lastname: Martini
authors.affiliation: Oncologia Medica, Dipartimento di Internistica Clinica e Sperimentale "F. Magrassi ", Seconda Università degli Studi di Napoli, Napoli, Italia.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cardone
authors.affiliation: Oncologia Medica, Dipartimento di Internistica Clinica e Sperimentale "F. Magrassi ", Seconda Università degli Studi di Napoli, Napoli, Italia.
authors.forename: Teresa
authors.initials: T
authors.lastname: Troiani
authors.affiliation: Dipartimento di Patologia Diagnostica e di Laboratorio, Istituto Nazionale Tumori- IRCCS "Fondazione G. Pascale", Napoli, Italia.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Liguori
authors.affiliation: Oncologia Medica, Dipartimento di Internistica Clinica e Sperimentale "F. Magrassi ", Seconda Università degli Studi di Napoli, Napoli, Italia.
authors.forename: Donata
authors.initials: D
authors.lastname: Vitagliano
authors.affiliation: Oncologia Medica, Dipartimento di Internistica Clinica e Sperimentale "F. Magrassi ", Seconda Università degli Studi di Napoli, Napoli, Italia.
authors.forename: Stefania
authors.initials: S
authors.lastname: Napolitano
authors.affiliation: Oncologia Medica, Dipartimento di Internistica Clinica e Sperimentale "F. Magrassi ", Seconda Università degli Studi di Napoli, Napoli, Italia.
authors.forename: Floriana
authors.initials: F
authors.lastname: Morgillo
authors.affiliation: Sezione di Farmacologia, Dipartimento di Medicina Sperimentale, Seconda Università degli Studi di Napoli, Napoli, Italia.
authors.forename: Barbara
authors.initials: B
authors.lastname: Rinaldi
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche/Istituto di Endocrinologia ed Oncologia Sperimentale del CNR "G. Salvatore", Napoli, Italia.
authors.forename: Rosa Marina
authors.initials: RM
authors.lastname: Melillo
authors.affiliation: Dipartimento di Medicina Molecolare e Biotecnologie Mediche/Istituto di Endocrinologia ed Oncologia Sperimentale del CNR "G. Salvatore", Napoli, Italia.
authors.forename: Federica
authors.initials: F
authors.lastname: Liotti
authors.affiliation: Oncologia Medica A, Istituto Nazionale Tumori- IRCCS "Fondazione G. Pascale", Napoli, Italia.
authors.forename: Anna
authors.initials: A
authors.lastname: Nappi
authors.affiliation: Oncologia Medica, Dipartimento di Medicina Clinica e Chirurgica, Università Federico II di Napoli, Napoli, Italia.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bianco
authors.affiliation: Sezione di Farmacologia, Dipartimento di Medicina Sperimentale, Seconda Università degli Studi di Napoli, Napoli, Italia.
authors.forename: Liberato
authors.initials: L
authors.lastname: Berrino
authors.affiliation: Sezione di Farmacologia, Dipartimento di Medicina Sperimentale, Seconda Università degli Studi di Napoli, Napoli, Italia.
authors.forename: Loreta Pia
authors.initials: LP
authors.lastname: Ciuffreda
authors.affiliation: Oncologia Medica, Dipartimento di Internistica Clinica e Sperimentale "F. Magrassi ", Seconda Università degli Studi di Napoli, Napoli, Italia.
authors.forename: Davide
authors.initials: D
authors.lastname: Ciardiello
authors.affiliation: Oncologia Medica A, Istituto Nazionale Tumori- IRCCS "Fondazione G. Pascale", Napoli, Italia.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Iaffaioli
authors.affiliation: Dipartimento di Patologia Diagnostica e di Laboratorio, Istituto Nazionale Tumori- IRCCS "Fondazione G. Pascale", Napoli, Italia.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.affiliation: Sezione di Farmacologia, Dipartimento di Medicina Sperimentale, Seconda Università degli Studi di Napoli, Napoli, Italia.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Ferraiolo
authors.affiliation: Oncologia Medica, Dipartimento di Internistica Clinica e Sperimentale "F. Magrassi ", Seconda Università degli Studi di Napoli, Napoli, Italia.
authors.forename: Fortunato
authors.initials: F
authors.lastname: Ciardiello
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000813:Anilides / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D020868:Gene Silencing; D045325:HCT116 Cells; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism; D011804:Quinolines / Q000737:chemistry; D034622:RNA Interference; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry* / Q000378:metabolism; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D036341:Intercellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D011804:Quinolines; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C544831:GSK 1363089
keywords: AXL; FISH; GAS6; Pathology Section; colorectal cancer; foretinib