Linked Life Data

21775522

Source:http://linkedlifedata.com/resource/pubmed/id/21775522

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2011-9-1
pubmed:abstractText
The extracellular matrix protein TGFBI enhances the cytotoxic response of cancer cells to paclitaxel by affecting integrin signals that stabilize microtubules. Extending the implications of this knowledge, we tested the more general hypothesis that cancer cell signals which increase microtubule stability before exposure to paclitaxel may increase its ability to stabilize microtubules and thereby enhance its cytotoxicity. Toward this end, we carried out an siRNA screen to evaluate how genetic depletion affected microtubule stabilization, cell viability, and apoptosis. High content microscopic analysis was carried out in the absence or presence of paclitaxel. Kinase knockdowns that stabilized microtubules strongly enhanced the effects of paclitaxel treatment. Conversely, kinase knockdowns that enhanced paclitaxel-mediated cytotoxicity sensitized cells to microtubule stabilization by paclitaxel. The siRNA screen identified several genes that have not been linked previously to microtubule regulation or paclitaxel response. Gene shaving and Bayesian resampling used to classify these genes suggested three pathways of paclitaxel-induced cell death related to apoptosis and microtubule stability, apoptosis alone, or neither process. Our results offer a functional classification of the genetic basis for paclitaxel sensitivity and they support the hypothesis that stabilizing microtubules prior to therapy could enhance antitumor responses to paclitaxel treatment.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1538-7445
pubmed:author
pubmed:copyrightInfo
©2011 AACR.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5806-17
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Modulating microtubule stability enhances the cytotoxic response of cancer cells to Paclitaxel.
pubmed:affiliation
Department of Experimental Therapeutics, MD Anderson Cancer Center, University of Texas, Houston, Texas, USA. rbast@mdanderson.org
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural