Overexpression of cortactin in head and neck squamous cell carcinomas can be uncoupled from augmented EGF receptor expression

Autor: Sébastien Cagnol, Fabio Stanchi, Gérard Milano, Ellen Van Obberghen-Schilling, Marie-Christine Brunstein, Dominique Grall, Alexandre Bozec, Anne Sudaka, Ivana Fantozzi, Jean-Louis Fischel
Přispěvatelé: Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Unité de ciblage pharmacologique dans les cancers ORL, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Oncology
medicine.medical_specialty
Receptor expression
Blotting
Western
Cell
Fluorescent Antibody Technique
Mice
Nude
[SDV.CAN]Life Sciences [q-bio]/Cancer
macromolecular substances
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Kidney
Immunoenzyme Techniques
Mice
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Internal medicine
medicine
Animals
Humans
Gene silencing
Radiology
Nuclear Medicine and imaging
RNA
Messenger
Epidermal growth factor receptor
RNA
Small Interfering
Cells
Cultured
030304 developmental biology
0303 health sciences
biology
business.industry
Gene Amplification
Kidney metabolism
Hematology
General Medicine
ErbB Receptors
Blotting
Southern
medicine.anatomical_structure
Head and Neck Neoplasms
030220 oncology & carcinogenesis
Carcinoma
Squamous Cell
biology.protein
Female
business
Cortactin
Proto-oncogene tyrosine-protein kinase Src
Zdroj: Langenbeck's Archives of Surgery
Langenbeck's Archives of Surgery, Springer Verlag, 2008, pp.1-11. ⟨10.1080/02841860802089801⟩
ISSN: 1435-2443
1435-2451
DOI: 10.1080/02841860802089801⟩
Popis: Background. The gene encoding cortactin, CTTN (locus 11q13), an actin-binding substrate of Src kinases, is frequently amplified in breast and head and neck squamous cell carcinomas (HNSCC) and cortactin overexpression is thought to contribute in a significant way to the invasive phenotype of these tumors. Elevated Epidermal Growth Factor receptor (EGFR) expression is also commonly observed in HNSCC and has been associated with poor prognosis and resistance to cytotoxic agents, including ionizing radiation. It has been suggested that cortactin overexpression may increase EGFR levels in these tumors by affecting receptor downregulation, however we recently found by multivariate analysis, that cortactin expression status remained an independent prognostic factor for local recurrence, disease-free survival, and overall survival. Material and Methods. To examine the potential link between cortactin overexpression and EGFR status, we compared cortactin and EGFR levels in a series of tumor lines derived from HNSCC. RNAi-mediated silencing was performed in cortactin overexpressing cells and in vivo tumoral potential with respect to cortactin and EGFR status was analyzed. Results and Discussion. Cortactin and EGFR levels were not strictly coupled in these lines and cortactin depletion did not decrease steady state receptor levels, although it did affect the epithelial to mesenchymal phenotypic conversion of cells. These results, together with clinical findings point to the existence of an EGFR-independent role of cortactin in HNSCC that may have important implications regarding the design of targeted therapies to combat tumor spread.
Databáze: OpenAIRE
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