The mTORC2 component rictor contributes to cisplatin resistance in human ovarian cancer cells.

Resistance to cisplatin-based therapy is a major cause of treatment failure in human ovarian cancer. A better understanding of the mechanisms of cisplatin resistance will offer new insights for novel therapeutic strategies for this deadly disease. Akt and p53 are determinants of cisplatin sensitivit...

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Autores principales:	Akechai Im-aram, Lee Farrand, Seung-Min Bae, Gwonhwa Song, Yong Sang Song, Jae Yong Han, Benjamin K Tsang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/41842bf2483448daaa8c39c774903732
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spelling	oai:doaj.org-article:41842bf2483448daaa8c39c7749037322021-11-18T08:54:11ZThe mTORC2 component rictor contributes to cisplatin resistance in human ovarian cancer cells.1932-620310.1371/journal.pone.0075455https://doaj.org/article/41842bf2483448daaa8c39c7749037322013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24086535/?tool=EBIhttps://doaj.org/toc/1932-6203Resistance to cisplatin-based therapy is a major cause of treatment failure in human ovarian cancer. A better understanding of the mechanisms of cisplatin resistance will offer new insights for novel therapeutic strategies for this deadly disease. Akt and p53 are determinants of cisplatin sensitivity. Rictor is a component of mTOR protein kinase complex 2, which is required for Akt phosphorylation (Ser473) and full activation. However, the precise role of rictor and the relationship between rictor and p53 in cisplatin resistance remains poorly understood. Here, using sensitive wild-type p53 (OV2008 and A2780s), resistant wild-type p53 (C13* and OVCAR433), and p53 compromised (A2780cp, OCC1, and SKOV-3) ovarian cancer cells, we have demonstrated that (i) rictor is a determinant of cisplatin resistance in chemosensitive human ovarian cancer cells; (ii) cisplatin down-regulates rictor content by caspase-3 cleavage and proteasomal degradation; (iii) rictor down-regulation sensitizes chemo-resistant ovarian cancer cells to cisplatin-induced apoptosis in a p53-dependent manner; (iv) rictor suppresses cisplatin-induced apoptosis and confers resistance by activating and stabilizing Akt. These findings extend current knowledge on the molecular and cellular basis of cisplatin resistance and provide a rationale basis for rictor as a potential therapeutic target for chemoresistant ovarian cancer.Akechai Im-aramLee FarrandSeung-Min BaeGwonhwa SongYong Sang SongJae Yong HanBenjamin K TsangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e75455 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Akechai Im-aram Lee Farrand Seung-Min Bae Gwonhwa Song Yong Sang Song Jae Yong Han Benjamin K Tsang The mTORC2 component rictor contributes to cisplatin resistance in human ovarian cancer cells.
description	Resistance to cisplatin-based therapy is a major cause of treatment failure in human ovarian cancer. A better understanding of the mechanisms of cisplatin resistance will offer new insights for novel therapeutic strategies for this deadly disease. Akt and p53 are determinants of cisplatin sensitivity. Rictor is a component of mTOR protein kinase complex 2, which is required for Akt phosphorylation (Ser473) and full activation. However, the precise role of rictor and the relationship between rictor and p53 in cisplatin resistance remains poorly understood. Here, using sensitive wild-type p53 (OV2008 and A2780s), resistant wild-type p53 (C13* and OVCAR433), and p53 compromised (A2780cp, OCC1, and SKOV-3) ovarian cancer cells, we have demonstrated that (i) rictor is a determinant of cisplatin resistance in chemosensitive human ovarian cancer cells; (ii) cisplatin down-regulates rictor content by caspase-3 cleavage and proteasomal degradation; (iii) rictor down-regulation sensitizes chemo-resistant ovarian cancer cells to cisplatin-induced apoptosis in a p53-dependent manner; (iv) rictor suppresses cisplatin-induced apoptosis and confers resistance by activating and stabilizing Akt. These findings extend current knowledge on the molecular and cellular basis of cisplatin resistance and provide a rationale basis for rictor as a potential therapeutic target for chemoresistant ovarian cancer.
format	article
author	Akechai Im-aram Lee Farrand Seung-Min Bae Gwonhwa Song Yong Sang Song Jae Yong Han Benjamin K Tsang
author_facet	Akechai Im-aram Lee Farrand Seung-Min Bae Gwonhwa Song Yong Sang Song Jae Yong Han Benjamin K Tsang
author_sort	Akechai Im-aram
title	The mTORC2 component rictor contributes to cisplatin resistance in human ovarian cancer cells.
title_short	The mTORC2 component rictor contributes to cisplatin resistance in human ovarian cancer cells.
title_full	The mTORC2 component rictor contributes to cisplatin resistance in human ovarian cancer cells.
title_fullStr	The mTORC2 component rictor contributes to cisplatin resistance in human ovarian cancer cells.
title_full_unstemmed	The mTORC2 component rictor contributes to cisplatin resistance in human ovarian cancer cells.
title_sort	mtorc2 component rictor contributes to cisplatin resistance in human ovarian cancer cells.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/41842bf2483448daaa8c39c774903732
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The mTORC2 component rictor contributes to cisplatin resistance in human ovarian cancer cells.

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