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Conference Paper: c-Met overexpression contributes to the acquired apoptosis resistance of non-adherent ovarian cancer cells through a cross-talk mediated by phosphatidylinositol 3-kinase and extracellular signal-regulated kinase 1/2

Titlec-Met overexpression contributes to the acquired apoptosis resistance of non-adherent ovarian cancer cells through a cross-talk mediated by phosphatidylinositol 3-kinase and extracellular signal-regulated kinase 1/2
Authors
Issue Date2010
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://www.aacrmeetingabstracts.org/
Citation
The 101st Annual Meeting of the American Association for Cancer Research (AACR 2010), Washington DC., 17-21 April 2010. In AACR Meeting Abstracts, 2010 How to Cite?
AbstractOvarian cancer is the most lethal gynecological cancer mainly due to widespread peritoneal dissemination and malignant ascites. Key to this is the capacity of tumor cells to escape suspension-induced apoptosis (anoikis), which also underlies their resistance to chemotherapy. Here we utilized a non-adherent cell culture model to investigate molecular mechanisms of apoptotic resistance of ovarian cancer cells that may mimic the chemoresistance found in solid tumors. We found that ovarian cancer cells acquired a remarkable resistance to anoikis and apoptosis induced by exposure to clinically relevant doses of two front-line chemotherapeutic drugs cisplatin and paclitaxel when grown in three-dimensional (3D) than monolayer cultures. Inhibition of the hepatocyte growth factor (HGF) receptor c-Met, which is frequently overexpressed in ovarian cancer, by a specific inhibitor or small interfering RNA blocked the acquired anoikis resistance and restored chemosensitivity in 3D, not in 2D cultures. These effects were found to be dependent on both phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular-signal regulated kinase (ERK) 1/2 signaling pathways. Inhibitors of PI3K/Akt abrogated ERK1/2 activation and its associated anoikis resistance in response to HGF, suggesting a signaling relay between these two pathways. Furthermore, we identified, as a mechanism of this cross-talk, a central role of Ras. Interestingly, Ras did not lie upstream of PI3K/Akt, whereas PI3K/Akt signaling to ERK1/2 involved Ras. These findings shed new light on the apoptotic resistance mechanism of non-adherent ovarian cancer ascites cells.
DescriptionPoster Session 29 - Receptor Signaling in Endocrine Related Cancers: abstract no. 1722
Persistent Identifierhttp://hdl.handle.net/10722/127809
ISSN

 

DC FieldValueLanguage
dc.contributor.authorTang, MKSen_HK
dc.contributor.authorZhou, HYen_HK
dc.contributor.authorYam, JWPen_HK
dc.contributor.authorWong, ASTen_HK
dc.date.accessioned2010-10-31T13:47:48Z-
dc.date.available2010-10-31T13:47:48Z-
dc.date.issued2010en_HK
dc.identifier.citationThe 101st Annual Meeting of the American Association for Cancer Research (AACR 2010), Washington DC., 17-21 April 2010. In AACR Meeting Abstracts, 2010en_HK
dc.identifier.issn1948-3279-
dc.identifier.urihttp://hdl.handle.net/10722/127809-
dc.descriptionPoster Session 29 - Receptor Signaling in Endocrine Related Cancers: abstract no. 1722-
dc.description.abstractOvarian cancer is the most lethal gynecological cancer mainly due to widespread peritoneal dissemination and malignant ascites. Key to this is the capacity of tumor cells to escape suspension-induced apoptosis (anoikis), which also underlies their resistance to chemotherapy. Here we utilized a non-adherent cell culture model to investigate molecular mechanisms of apoptotic resistance of ovarian cancer cells that may mimic the chemoresistance found in solid tumors. We found that ovarian cancer cells acquired a remarkable resistance to anoikis and apoptosis induced by exposure to clinically relevant doses of two front-line chemotherapeutic drugs cisplatin and paclitaxel when grown in three-dimensional (3D) than monolayer cultures. Inhibition of the hepatocyte growth factor (HGF) receptor c-Met, which is frequently overexpressed in ovarian cancer, by a specific inhibitor or small interfering RNA blocked the acquired anoikis resistance and restored chemosensitivity in 3D, not in 2D cultures. These effects were found to be dependent on both phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular-signal regulated kinase (ERK) 1/2 signaling pathways. Inhibitors of PI3K/Akt abrogated ERK1/2 activation and its associated anoikis resistance in response to HGF, suggesting a signaling relay between these two pathways. Furthermore, we identified, as a mechanism of this cross-talk, a central role of Ras. Interestingly, Ras did not lie upstream of PI3K/Akt, whereas PI3K/Akt signaling to ERK1/2 involved Ras. These findings shed new light on the apoptotic resistance mechanism of non-adherent ovarian cancer ascites cells.-
dc.languageengen_HK
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://www.aacrmeetingabstracts.org/-
dc.relation.ispartofAACR Meeting Abstracts-
dc.titlec-Met overexpression contributes to the acquired apoptosis resistance of non-adherent ovarian cancer cells through a cross-talk mediated by phosphatidylinositol 3-kinase and extracellular signal-regulated kinase 1/2en_HK
dc.typeConference_Paperen_HK
dc.identifier.emailYam, JWP: judyyam@pathology.hku.hken_HK
dc.identifier.emailWong, AST: awong1@hkucc.hku.hken_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros174126en_HK
dc.publisher.placeUnited States-
dc.description.otherThe 101st Annual Meeting of the American Association for Cancer Research (AACR 2010), Washington D.C., 17-21 April 2010. In AACR Meeting Abstracts, 2010-

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