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AXL is an oncotarget in human colorectal cancer.
- Source :
-
Oncotarget [Oncotarget] 2015 Sep 15; Vol. 6 (27), pp. 23281-96. - Publication Year :
- 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.
- Subjects :
- Adult
Aged
Aged, 80 and over
Anilides chemistry
Animals
Antineoplastic Agents chemistry
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cell Survival
Female
Gene Silencing
HCT116 Cells
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Intercellular Signaling Peptides and Proteins metabolism
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Neoplasm Transplantation
Neovascularization, Pathologic
Oligonucleotide Array Sequence Analysis
Proto-Oncogene Proteins metabolism
Quinolines chemistry
RNA Interference
Receptor Protein-Tyrosine Kinases metabolism
Axl Receptor Tyrosine Kinase
Colorectal Neoplasms drug therapy
Colorectal Neoplasms metabolism
Proto-Oncogene Proteins chemistry
Receptor Protein-Tyrosine Kinases chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1949-2553
- Volume :
- 6
- Issue :
- 27
- Database :
- MEDLINE
- Journal :
- Oncotarget
- Publication Type :
- Academic Journal
- Accession number :
- 25966280
- Full Text :
- https://doi.org/10.18632/oncotarget.3962