Details
- Autor(en) / Beteiligte
- Titel
- AXL receptor kinase is a mediator of YAP-dependent oncogenic functions in hepatocellular carcinoma
- Ist Teil von
- Oncogene, 2011-03, Vol.30 (10), p.1229-1240
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Yes-associated protein (YAP) is a downstream effector of the Hippo signaling pathway, which controls organ expansion and tissue development. We have recently defined the tumorigenic potential and clinical significance of the YAP1 oncogene in human hepatocellular carcinoma (HCC). The present study aims to define the tumorigenic properties of YAP in HCC and elucidate the related downstream signaling mechanism. In a gain-of-function study, we demonstrated that ectopic increased expression of YAP in the immortalized non-tumorigenic hepatocyte cell line MIHA confers tumorigenic and metastatic potentials, as evidenced by (1) enhanced aptitudes in cell viability, anchorage-independent growth, migration and invasion; (2) tumor formation in a xenograft mouse model; and (3) induction of HCC biomarker α-fetoprotein and activation of mitogen-activated protein kinase. Furthermore, we have identified AXL, a receptor tyrosine kinase, as a key downstream target that drives YAP-dependent oncogenic functions. RNAi-mediated knockdown of AXL expression decreased the ability of YAP-expressing MIHA cells and of the primary HCC cell line to proliferate and invade. These results indicate that AXL is a mediator of YAP-dependent oncogenic activities and implicates it as a potential therapeutic target for HCC.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0950-9232eISSN: 1476-5594DOI: 10.1038/onc.2010.504Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3330262
- Format
- –
- Schlagworte
- 631/80/86, 692/699/67/1504/1610, 692/699/67/395, Animals, Apoptosis, Axl protein, Axl Receptor Tyrosine Kinase, Biological and medical sciences, Carcinoma, Hepatocellular - genetics, Carcinoma, Hepatocellular - metabolism, Cell Biology, Cell Cycle Proteins, Cell growth, Cell Line, Cell Movement - genetics, Cell physiology, Cell Proliferation, Cell receptors, Cell structures and functions, Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes, Cell Transformation, Neoplastic - genetics, Cell Transformation, Neoplastic - metabolism, Cell viability, Fundamental and applied biological sciences. Psychology, Gastroenterology. Liver. Pancreas. Abdomen, Gene Expression, Gene Expression Regulation, Neoplastic - genetics, Gene Knockdown Techniques, Genetic aspects, Health aspects, Hepatocellular carcinoma, Hepatoma, Human Genetics, Humans, Immunoblotting, Internal Medicine, Kinases, Liver cancer, Liver Neoplasms - genetics, Liver Neoplasms - metabolism, Liver. Biliary tract. Portal circulation. Exocrine pancreas, Male, MAP kinase, Medical sciences, Medicine, Medicine & Public Health, Metastases, Mice, Mice, Nude, Miscellaneous, Molecular and cellular biology, Nuclear Proteins - genetics, Nuclear Proteins - metabolism, Oligonucleotide Array Sequence Analysis, Oncogenes, Oncology, original-article, Physiological aspects, Protein kinases, Protein-tyrosine kinase receptors, Proto-Oncogene Proteins - genetics, Proto-Oncogene Proteins - metabolism, Receptor Protein-Tyrosine Kinases - genetics, Receptor Protein-Tyrosine Kinases - metabolism, Reverse Transcriptase Polymerase Chain Reaction, RNA, Small Interfering, RNA-mediated interference, Signal transduction, Signal Transduction - physiology, Therapeutic targets, Transcription Factors - genetics, Transcription Factors - metabolism, Transfection, Transplantation, Heterologous, Tumors, Xenografts, Yes-associated protein, α-Fetoprotein