KiSS1 suppresses TNFalpha-induced breast cancer cell invasion via an inhibition of RhoA-mediated NF-kappaB activation.
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 proliferation. Furthermore, KP10 inhibited TNFalpha-induced cell migration and RhoA GTPase activation. Therefore, our data demonstrate that KiSS1 inhibits TNFalpha-induced NF-kappaB activation via downregulation of RhoA activation and suppression of breast cancer cell migration and invasion.
Cho
Sung-Gook
SG
Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, Texas 77030, USA.
Li
Dali
D
Stafford
Lewis J
LJ
Luo
Jian
J
Rodriguez-Villanueva
Melissa
M
Wang
Ying
Y
Liu
Mingyao
M
D001943:Breast Neoplasms / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D006801:Humans; D059648:Kisspeptins; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009842:Oligopeptides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors*
C106628:KISS1 protein, human; D059648:Kisspeptins; D016328:NF-kappa B; D009842:Oligopeptides; D014409:Tumor Necrosis Factor-alpha; D025521:Tumor Suppressor Proteins; D020742:rhoA GTP-Binding Protein