KiSS1 suppresses TNFα-induced breast cancer cell invasion via an inhibition of RhoA-Mediated NF-κB activation
✍ Scribed by Sung-Gook Cho; Dali Li; Lewis J. Stafford; Jian Luo; Melissa Rodriguez-Villanueva; Ying Wang; Mingyao Liu
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 324 KB
- Volume
- 107
- Category
- Article
- ISSN
- 0730-2312
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
Tumor necrosis factor‐alpha (TNFα) induces cancer development and metastasis, which is prominently achieved by nuclear factor‐kappa B (NF‐κB) activation. TNFα‐induced NF‐κB 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 TNFα‐induced NF‐κB activation and further tumor cell migration. In this study, we demonstrate that KiSS1 suppresses the migration of breast cancer cells by inhibiting TNFα‐induced NF‐κB pathway and RhoA activation. Both KiSS1 overexpression and KP10 (kisspeptin‐10) stimulation inhibited TNFα‐induced NF‐κB activity, suppressed TNFα‐induced cell migration and cell attachment to fibronectin in breast cancer cells while KP10 has little effect on cancer cell proliferation. Furthermore, KP10 inhibited TNFα‐induced cell migration and RhoA GTPase activation. Therefore, our data demonstrate that KiSS1 inhibits TNFα‐induced NF‐κB activation via downregulation of RhoA activation and suppression of breast cancer cell migration and invasion. J. Cell. Biochem. 107: 1139–1149, 2009. © 2009 Wiley‐Liss, Inc.