TY - JOUR
T1 - AXL is an oncotarget in human colorectal cancer
AU - Martinelli, Erika
AU - Martini, Giulia
AU - Cardone, Claudia
AU - Troiani, Teresa
AU - Liguori, Giuseppina
AU - Vitagliano, Donata
AU - Napolitano, Stefania
AU - Morgillo, Floriana
AU - Rinaldi, Barbara
AU - Melillo, Rosa Marina
AU - Liotti, Federica
AU - Nappi, Anna
AU - Bianco, Roberto
AU - Berrino, Liberato
AU - Ciuffreda, Loreta Pia
AU - Ciardiello, Davide
AU - Iaffaioli, Vincenzo
AU - Botti, Gerardo
AU - Ferraiolo, Fiorella
AU - Ciardiello, Fortunato
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
KW - AXL
KW - Colorectal cancer
KW - FISH
KW - Foretinib
KW - GAS6
UR - http://www.scopus.com/inward/record.url?scp=84943411277&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84943411277&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.3962
DO - 10.18632/oncotarget.3962
M3 - Article
AN - SCOPUS:84943411277
VL - 6
SP - 23281
EP - 23296
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 27
ER -