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.
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.
Authors: Jan Sperveslage; Konrad Steinestel; Katharina Stock; Rebekka Borrink; Jan-Henrik Mikesch; Anna Hansmeier; Jan Rehkämper; Marcel Trautmann; Eva Wardelmann; Wolfgang Hartmann Journal: Cancer Cell Int Date: 2019-03-29 Impact factor: 5.722