S-Space Graduate School of Convergence Science and Technology (융합과학기술대학원) Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과) Journal Papers (저널논문_분자의학 및 바이오제약학과)
Curcumin Prevents Palmitoylation of Integrin beta 4 in Breast Cancer Cells
- Coleman, David T.; Soung, Young Hwa; Surh, Young-Joon; Cardelli, James A.; Chung, Jun
- Issue Date
- PLoS ONE, Vol.10 No.5, p. e0125399
- Curcumin has been shown to mitigate cancer phenotypes such as invasive migration, proliferation, and survival by disrupting numerous signaling pathways. Our previous studies showed that curcumin inhibits integrin beta 4 (ITG beta 4)-dependent migration by blocking interaction of this integrin with growth factor receptors in lipid rafts. In the current study, we investigated the possibility that curcumin inhibits ITG beta 4 palmitoylation, a post-translational modification required for its lipid raft localization and signaling activity. We found that the levels of ITG beta 4 palmitoylation correlated with the invasive potential of breast cancer cells, and that curcumin effectively reduced the levels of ITG beta 4 palmitoylation in invasive breast cancer cells. Through studies of ITG beta 4 palmitoylation kinetics, we concluded curcumin suppressed palmitoylation independent of growth factor-induced phosphorylation of key ITG beta 4 Ser and Tyr residues. Rather, curcumin blocked autoacylation of the palmitoyl acyltransferase DHHC3 that is responsible for ITG beta 4 palmitoylation. Moreover, these data reveal that curcumin is able to prevent the palmitoylation of a subset of proteins, but not indiscriminately bind to and block all cysteines from modifications. Our studies reveal a novel paradigm for curcumin to account for much of its biological activity, and specifically, how it is able to suppress the signaling function of ITG beta 4 in breast cancer cells.
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