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dc.contributor.authorYu, Yu
dc.contributor.authorGaillard, S.
dc.contributor.authorPhillip, J.
dc.contributor.authorHuang, T.
dc.contributor.authorPinto, S.
dc.contributor.authorTessarollo, N.
dc.contributor.authorZhang, Z.
dc.contributor.authorPandey, A.
dc.contributor.authorWirtz, D.
dc.contributor.authorAyhan, A.
dc.contributor.authorDavidson, B.
dc.contributor.authorWang, T.
dc.contributor.authorShih, I.
dc.date.accessioned2017-01-30T12:27:16Z
dc.date.available2017-01-30T12:27:16Z
dc.date.created2017-01-17T19:30:21Z
dc.date.issued2015
dc.identifier.citationYu, Y. and Gaillard, S. and Phillip, J. and Huang, T. and Pinto, S. and Tessarollo, N. and Zhang, Z. et al. 2015. Inhibition of Spleen Tyrosine Kinase Potentiates Paclitaxel-Induced Cytotoxicity in Ovarian Cancer Cells by Stabilizing Microtubules. Cancer Cell. 28 (1): pp. 82-96.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/21755
dc.identifier.doi10.1016/j.ccell.2015.05.009
dc.description.abstract

Resistance to chemotherapy represents a major obstacle for long-term remission, and effective strategies toovercome drug resistance would have significant clinical impact. We report that recurrent ovarian carcinomas after paclitaxel/carboplatin treatment have higher levels of spleen tyrosine kinase (SYK) and phospho-SYK. Invitro, paclitaxel-resistant cells expressed higher SYK, and the ratio of phospho-SYK/SYK positively associated with paclitaxel resistance in ovarian cancer cells. Inactivation of SYK by inhibitors or gene knockdown sensitized paclitaxel cytotoxicity invitro and invivo. Analysis of the phosphotyrosine proteome in paclitaxel-resistant tumor cells revealed that SYK phosphorylates tubulins and microtubule-associated proteins. Inhibition of SYK enhanced microtubule stability in paclitaxel-resistant tumor cells that were otherwise insensitive. Thus, targeting SYK pathway is a promising strategy to enhance paclitaxel response.

dc.titleInhibition of Spleen Tyrosine Kinase Potentiates Paclitaxel-Induced Cytotoxicity in Ovarian Cancer Cells by Stabilizing Microtubules
dc.typeJournal Article
dcterms.source.volume28
dcterms.source.number1
dcterms.source.startPage82
dcterms.source.endPage96
dcterms.source.issn1535-6108
dcterms.source.titleCancer Cell
curtin.departmentSchool of Pharmacy
curtin.accessStatusOpen access via publisher


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