Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/26750

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Title
A CD44 survival pathway triggers chemoresistance via lyn kinase and phosphoinositide 3-kinase/Akt in colon carcinoma cells
Author/Creator
Bates, Richard C.;  Edwards, Nathaniel S.;  Burns, Gordon F.;  Fisher, David E.
Description
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Description
A major obstacle to successful treatment of colorectal cancer is chemotherapy resistance. Enhanced expression of variant CD44 isoforms has been associated with aggressive tumor behavior, prompting the question of whether signaling from this receptor might modulate drug sensitivity. Activation of variant CD44 in colon carcinoma cell lines triggered resistance to the drug 1,3-bis(2-chloroethyl)-1-nitrosurea. Resistance was induced by monoclonal antibodies directed against epitopes independent of the hyaluronate-binding region but was not triggered by identical treatment of a carcinoma line expressing the standard CD44 isoform. We observed that variant CD44 produced activation of the src-family tyrosine kinase lyn. Moreover, overexpression of dominant-active lyn recapitulated chemoresistance via a pathway shown to involve activation of phosphoinositide 3-kinase and Akt. These results establish a novel role for CD44 in determining survival of colon carcinoma cells through lyn kinase and Akt. The ability to suppress apoptosis might play a critical role in the onset and development of colorectal malignancies.
Relation
Cancer Research Vol. 61, Issue 13, p. 5275-5283
Relation
http://cancerres.aacrjournals.org/cgi/content/abstract/61/13/5275
Date
2001
Publisher
American Association Cancer Research
Keyword(s)
CD44;  chemoresistance;  lyn kinase;  phosphoinositide 3-kinase;  Akt;  colon carcinoma cells
Resource Type
journal article
Identifier
http://hdl.handle.net/1959.13/26750
Identifier
ISSN:0008-5472
Reviewed
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Subject
"Cancer Research"
 
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