PMID- 21544801 OWN - NLM STAT- MEDLINE DCOM- 20111220 LR - 20211020 IS - 1097-0215 (Electronic) IS - 0020-7136 (Print) IS - 0020-7136 (Linking) VI - 129 IP - 12 DP - 2011 Dec 15 TI - Functional interrelationship between the WASF3 and KISS1 metastasis-associated genes in breast cancer cells. PG - 2825-35 LID - 10.1002/ijc.25964 [doi] AB - Loss of WASF3 function in breast cancer cells results in loss of invasion phenotypes and reduced metastatic potential. By using oligonucleotide arrays, we now demonstrate that knockdown of WASF3 leads to the upregulation of the KISS1 metastasis suppressor gene with concomitant reduced invasion and loss of matrix metalloproteinases (MMP)-9 activity. Using a luciferase reporter, KISS1 transcription is significantly increased in the absence of WASF3. Knockdown of KISS1 in WASF3-silenced cells resulted in the recovery of the invasion phenotype. WASF3 knockdown also resulted in elevated IkappaBalpha levels in the cytoplasm and reduced levels of nuclear factor-kappa-B (NF-kappaB) p65/50 subunits in the nucleus. Tumor necrosis factor-alpha (TNF-alpha) has been associated with cell invasion through induction of MMP-9 production via KISS1 regulation of the NF-kappaB pathway. When WASF3 knockdown cells are treated with TNF-alpha, no effect is seen on invasion or nuclear translocation of NF-kappaB. Thus, coordinated expression patterns of the WASF3 metastasis promoter gene and the KISS1 metastasis suppressor gene appear to exert their influence through inhibition of NF-kappaB signaling, which in turn regulates MMP-9 production facilitating invasion. CI - Copyright (c) 2011 UICC. FAU - Teng, Yong AU - Teng Y AD - School of Medicine, Medical College of Georgia, Augusta, GA, USA. FAU - Liu, Mingyao AU - Liu M FAU - Cowell, John K AU - Cowell JK LA - eng GR - R01 CA120510/CA/NCI NIH HHS/United States GR - R01 CA120510-01A1/CA/NCI NIH HHS/United States GR - CA120510/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110505 PL - United States TA - Int J Cancer JT - International journal of cancer JID - 0042124 RN - 0 (KISS1 protein, human) RN - 0 (Kisspeptins) RN - 0 (NF-kappa B) RN - 0 (WASF3 protein, human) RN - 0 (Wiskott-Aldrich Syndrome Protein Family) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) SB - IM MH - Breast Neoplasms/*genetics MH - Cell Line, Tumor MH - Cell Movement MH - Female MH - Gene Knockdown Techniques MH - Humans MH - Kisspeptins/*genetics/metabolism MH - Male MH - Matrix Metalloproteinase 9/metabolism MH - NF-kappa B/metabolism MH - Neoplasm Invasiveness MH - Neoplasm Metastasis/*genetics MH - Prostatic Neoplasms/metabolism MH - Signal Transduction/genetics MH - Up-Regulation MH - Wiskott-Aldrich Syndrome Protein Family/*genetics/metabolism PMC - PMC3154992 MID - NIHMS275139 EDAT- 2011/05/06 06:00 MHDA- 2011/12/21 06:00 PMCR- 2012/12/15 CRDT- 2011/05/06 06:00 PHST- 2010/11/02 00:00 [received] PHST- 2011/01/12 00:00 [accepted] PHST- 2011/05/06 06:00 [entrez] PHST- 2011/05/06 06:00 [pubmed] PHST- 2011/12/21 06:00 [medline] PHST- 2012/12/15 00:00 [pmc-release] AID - 10.1002/ijc.25964 [doi] PST - ppublish SO - Int J Cancer. 2011 Dec 15;129(12):2825-35. doi: 10.1002/ijc.25964. Epub 2011 May 5.