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Suppression of phospho-p85α-GTP-Rac1 lipid raft interaction by bichalcone analog attenuates cancer cell invasion
- Source :
- Molecular carcinogenesis. 55(12)
- Publication Year :
- 2015
-
Abstract
- The p85α subunit of phosphatidylinositol 3-kinase (PI3K) acts as a key regulator of cell proliferation and motility, which mediates signals that confer chemoresistance to many human cancer cells. Using small interfering RNAs against matrix metalloproteinase-2 (MMP-2) and the MMP-2 promoter-driven luciferase assay, we showed that the new synthetic bichalcone analog TSWU-CD4 inhibits the invasion of human cancer cells by down-regulating MMP-2 expression. Treatment with TSWU-CD4 inhibited MMP-2 expression and cell invasion, which were restored by ectopic wild type (wt) p85α or a constitutively active form of MAPK kinase 3 (CA MKK3), CA MKK6, or CA p38α mitogen-activated protein kinase (MAPK). The attenuated formation of lipid raft-associated phospho (p)-p85α-GTP-Rac1 complexes, protein kinase B (Akt) Ser 473 phosphorylation, and cell invasion by TSWU-CD4 was reversed by overexpression of wt p85α or the p85α Brc-homology (BH) domain. The ectopic expression of CA Rac1
Details
- ISSN :
- 10982744
- Volume :
- 55
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Molecular carcinogenesis
- Accession number :
- edsair.pmid..........391128158e7d96ab042c54dbb7b77e09