TY - JOUR
T1 - Epidermal growth factor-induced ovarian carcinoma cell migration is associated with JAK2/STAT3 signals and changes in the abundance and localization of a6?1 integrin
AU - Magee, Michelle
AU - Findlay, John (Jock) K
AU - Ackland, Margaret Leigh
AU - Ahmed, Nuzhat
PY - 2009
Y1 - 2009
N2 - Peritoneal dissemination of ovarian carcinoma is mediated by epithelial-mesenchymal interconversions leading to the disruption of cell-cell contact and modulation of cell-extracellular matrix (ECM) interactions. The present study was designed to evaluate the effects of epidermal growth factor (EGF) as a modulator of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) signalling and changes in integrin expression during the process similar to EMT. A fibroblastic morphology with reduced intercellular cell contacts and increased cell motility was observed in ovarian cancer cell lines in response to EGF and was concomitant with the up regulation of EMT-associated N-cadherin and vimentin expression. These changes were accompanied by an increase in a2, a6 and ?1 integrin subunits and activation of JAK2 and STAT3 signalling which was suppressed by a specific JAK2 inhibitor. Consistent with the suppression of STAT3 activity, N-cadherin and vimentin expression were abrogated and was coherent with the loss of cell motility and the expression of a6 and ?1 integrin subunits. Neutralizing antibodies against a6 and ?1 subunits inhibited cancer cell migration. A strong correlation between the expression of N-cadherin, vimentin and JAK2/STAT3 levels were detected in high-grade ovarian tumors and was consistent with the previously reported enhanced expression of a6 integrin subunit in advanced tumors [Ahmed N, Riley C, Oliva K, Rice G, Quinn M. Ascites induces modulation of a6?1 integrin and urokinase plasminogen activator receptor expression and associated functions in ovarian carcinoma. British Journal of Cancer 2005;92:1475-85]. Our data incorporating the clinical samples and the cancer cell lines is the first to demonstrate that JAK2/STAT3 pathway may be one of the downstream events in EMT-like process and a6?1 integrin-mediated signalling in ovarian carcinomas
AB - Peritoneal dissemination of ovarian carcinoma is mediated by epithelial-mesenchymal interconversions leading to the disruption of cell-cell contact and modulation of cell-extracellular matrix (ECM) interactions. The present study was designed to evaluate the effects of epidermal growth factor (EGF) as a modulator of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) signalling and changes in integrin expression during the process similar to EMT. A fibroblastic morphology with reduced intercellular cell contacts and increased cell motility was observed in ovarian cancer cell lines in response to EGF and was concomitant with the up regulation of EMT-associated N-cadherin and vimentin expression. These changes were accompanied by an increase in a2, a6 and ?1 integrin subunits and activation of JAK2 and STAT3 signalling which was suppressed by a specific JAK2 inhibitor. Consistent with the suppression of STAT3 activity, N-cadherin and vimentin expression were abrogated and was coherent with the loss of cell motility and the expression of a6 and ?1 integrin subunits. Neutralizing antibodies against a6 and ?1 subunits inhibited cancer cell migration. A strong correlation between the expression of N-cadherin, vimentin and JAK2/STAT3 levels were detected in high-grade ovarian tumors and was consistent with the previously reported enhanced expression of a6 integrin subunit in advanced tumors [Ahmed N, Riley C, Oliva K, Rice G, Quinn M. Ascites induces modulation of a6?1 integrin and urokinase plasminogen activator receptor expression and associated functions in ovarian carcinoma. British Journal of Cancer 2005;92:1475-85]. Our data incorporating the clinical samples and the cancer cell lines is the first to demonstrate that JAK2/STAT3 pathway may be one of the downstream events in EMT-like process and a6?1 integrin-mediated signalling in ovarian carcinomas
UR - http://www.sciencedirect.com/science/article/pii/S1357272508003968
U2 - 10.1016/j.biocel.2008.09.018
DO - 10.1016/j.biocel.2008.09.018
M3 - Article
SN - 1357-2725
VL - 41
SP - 1034
EP - 1045
JO - International Journal of Biochemistry & Cell Biology
JF - International Journal of Biochemistry & Cell Biology
IS - 5
ER -
