Document Detail


Insight into the 6-thiopurine-mediated Termination of the Invasive Motility of Tumor Cells Derived From Inflammatory Breast Cancer.
MedLine Citation:
PMID:  21568348     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Our study showed that a combination of 6-thiopurine (6-TP) drugs and a redox agent effectively inhibits the motility of SUM cells derived from human inflammatory breast cancer (IBC) cells and RhoC-overexpressed mammary epithelium cells. This 6-TP-mediated inhibition of cell motility occurs because the treated 6-TPs target and inactivate RhoC. A molecular mechanism for inactivation by the 6-TP-mediated RhoC is proposed by which treated TPs are converted in cells into 6-thioguanosine phosphate (6-TGNP). This 6-TGNP in turn reacts with the Cys20 side chain of the redox-sensitive GXXXCGK(S/T)C motif of RhoC to produce a 6-TGNP-RhoC disulfide adduct. A redox agent synergistically enhances the formation process of this disulfide. The adduct that is formed impedes RhoC guanine nucleotide exchange, which populates an inactive RhoC. Our results suggest that 6-TGNP can also react with the redox-sensitive GXXXCGK(S/T)C and GXXXXGK(S/T)C motif of RhoA and Rac, respectively, to produce a 6-TGNP-RhoA and 6-TGNP-Rac disulfide adduct. However, given that RhoC has been shown to be overexpressed in ~90% of IBC lesions, the populated RhoC but not other Rho proteins is likely to be a primary target for 6-TPs and a redox agent to terminate the metastasis of IBC.
Authors:
Jongyun Heo; Michael Wey; Inpyo Hong
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-16
Journal Detail:
Title:  Biochemistry     Volume:  -     ISSN:  1520-4995     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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