Puberty Promoter (KISS1) May Also Suppress Breast Cancer Metastasis

[Rich66]

1: J Cell Biochem. 2009 Jun 16. [Epub ahead of print] Links

KiSS1 suppresses TNFalpha-induced breast cancer cell invasion via an inhibition of RhoA-Mediated NF-kappaB activation.

Cho SG, Li D, Stafford LJ, Luo J, Rodriguez-Villanueva M, Wang Y, Liu M.
Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, Texas 77030.
Tumor necrosis factor-alpha (TNFalpha) induces cancer development and metastasis, which is prominently achieved by nuclear factor-kappa B (NF-kappaB) activation. TNFalpha-induced NF-kappaB activation enhances cellular mechanisms including proliferation, migration, and invasion. KiSS1, a key regulator of puberty, was initially discovered as a tumor metastasis suppressor. The expression of KiSS1 was lost or down-regulated in different metastatic tumors. However, it is unclear whether KiSS1 regulates TNFalpha-induced NF-kappaB activation and further tumor cell migration. In this study, we demonstrate that KiSS1 suppresses the migration of breast cancer cells by inhibiting TNFalpha-induced NF-kappaB pathway and RhoA activation. Both KiSS1 overexpression and KP10 (kisspeptin-10) stimulation inhibited TNFalpha-induced NF-kappaB activity, suppressed TNFalpha-induced cell migration and cell attachment to fibronectin in breast cancer cells while KP10 has little effect on cancer cell prolife