期刊
SCIENTIFIC REPORTS
卷 5, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep09275
关键词
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资金
- Fundamental Research Funds for the Central Universities [XDJK2014C176]
- Start-up Foundation of Southwest University [SWU114017]
- National Natural Science Foundation of China [NSFC-81402393]
- U.S. National Institutes of Health [CA-125707]
- National Science Foundation [CBET-0729091]
- NATIONAL CANCER INSTITUTE [R01CA125707] Funding Source: NIH RePORTER
Nanoliposomal formulation of C-6-ceramide, a proapoptotic sphingolipid metabolite, presents an effective way to treat malignant tumor. Here, we provide evidence that acute treatment (30 min) of melanoma and breast cancer cells with nanoliposomal C-6-ceramide (NaL-C-6) may suppress cell migration without inducing cell death. By employing a novel flow migration assay, we demonstrated that NaL-C-6 decreased tumor extravasation under shear conditions. Compared with ghost nanoliposome, NaL-C-6 triggered phosphorylation of PI3K and PKC zeta and dephosphorylation of PKC alpha. Concomitantly, activated PKC zeta translocated into cell membrane. siRNA knockdown or pharmacological inhibition of PKC zeta or PI3K rescued NaL-C-6-mediated suppression of tumor migration. By inducing dephosphorylation of paxillin, PKC zeta was responsible for NaL-C-6-mediated stress fiber depolymerization and focal adhesion disassembly in the metastatic tumor cells. PKC zeta and PI3K regulated cell shear-resistant adhesion in a way that required integrin avb3 affinity modulation. In conclusion, we identified a novel role of acute nanoliposomal ceramide treatment in reducing integrin affinity and inhibiting melanoma metastasis by conferring PI3K and PKC zeta tumor-suppressive activities.
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