PMID- 18996214 OWN - NLM STAT- MEDLINE DCOM- 20090330 LR - 20181201 IS - 1095-8355 (Electronic) IS - 1065-6995 (Linking) VI - 33 IP - 2 DP - 2009 Feb TI - Multiple shRNA-mediated knockdown of TACE reduces the malignancy of HeLa cells. PG - 158-64 LID - 10.1016/j.cellbi.2008.10.008 [doi] AB - Tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE) is a key enzyme involved in the proteolytic shedding of the ectodomain of several membrane-bound growth factors, cytokines and receptors. Here, we constructed a multiple short hairpin RNA (shRNA) expression vector containing four shRNAs against TACE. We found that in HeLa cells our multiple shRNAs vector produced a higher level of TACE knockdown than any single shRNA vector containing only one TACE shRNA. Silencing TACE expression in HeLa cells decreased their malignancy by decreasing the proliferation, adhesion and migration, as well as inducing apoptosis in these cells. Furthermore, our data suggest that the effects of TACE on the malignancy of HeLa cells may be mediated via activation of the EGFR (epidermal growth factor receptor) signaling pathway. Our findings suggest that using a combination of shRNAs within one vector to silence the expression of TACE might be a potential therapeutic strategy for tumors. FAU - Yan, Yuan AU - Yan Y AD - Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China. FAU - Zhang, Jie AU - Zhang J FAU - Guo, Jian-Li AU - Guo JL FAU - Huang, Wei AU - Huang W FAU - Yang, Yu-Zhen AU - Yang YZ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20081101 PL - England TA - Cell Biol Int JT - Cell biology international JID - 9307129 RN - 0 (RNA, Untranslated) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 3.4.24.- (ADAM Proteins) RN - EC 3.4.24.86 (ADAM17 Protein) RN - EC 3.4.24.86 (ADAM17 protein, human) SB - IM MH - ADAM Proteins/*antagonists & inhibitors/genetics/metabolism MH - ADAM17 Protein MH - Apoptosis MH - ErbB Receptors/metabolism MH - Gene Knockdown Techniques MH - HeLa Cells MH - Humans MH - Neoplasms/*therapy MH - *RNA Interference MH - RNA, Untranslated/chemistry MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2008/11/11 09:00 MHDA- 2009/03/31 09:00 CRDT- 2008/11/11 09:00 PHST- 2008/05/26 00:00 [received] PHST- 2008/08/13 00:00 [revised] PHST- 2008/10/13 00:00 [accepted] PHST- 2008/11/11 09:00 [pubmed] PHST- 2009/03/31 09:00 [medline] PHST- 2008/11/11 09:00 [entrez] AID - S1065-6995(08)00601-X [pii] AID - 10.1016/j.cellbi.2008.10.008 [doi] PST - ppublish SO - Cell Biol Int. 2009 Feb;33(2):158-64. doi: 10.1016/j.cellbi.2008.10.008. Epub 2008 Nov 1.