PMID- 30714134 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230201 IS - 1097-4652 (Electronic) IS - 0021-9541 (Linking) VI - 234 IP - 9 DP - 2019 Sep TI - MMP2/3 promote the growth and migration of laryngeal squamous cell carcinoma via PI3K/Akt-NF-kappaB-mediated epithelial-mesenchymal transformation. PG - 15847-15855 LID - 10.1002/jcp.28242 [doi] AB - Laryngeal squamous cell carcinoma (LSCC) is an aggressive malignancy with metastatic potential and high mortality worldwide. Matrix metalloproteinases (MMPs) are a group of extracellular proteolytic enzymes. Although MMPs have been proved to be essential in the process of tumor migration and metastasis in most types of carcinomas, the expression and function of MMP2/3 in LSCC remain unknown. Here, we investigated the roles of MMP2/3 in LSCC and elucidated the underlying mechanism. We found that levels of MMP2/3 were significantly higher in clinical LSCC samples than in paired normal sample examined by real-time polymerase chain reaction and western blot assays. Moreover, overexpression of MMP2/3 promoted the proliferation and migration of LSCC cells by Cell Counting Kit-8, transwell, and scratch wound-healing assays in vitro. Furthermore, levels of epithelial cell markers (E-cadherin and occludin) were decreased following MMP2/3 overexpression, with increased levels of mesenchymal cell markers (N-cadherin and vimentin), suggesting the involvement of epithelial-mesenchymal transformation (EMT) process in MMP2/3-mediated LSCC cell migration. By using short hairpin RNA, knockdown of MMP2/3 expression inhibited the proliferation, migration, and EMT process in LSCC cells in vitro. More importantly, we confirmed that MMP2/3 promoted LSCC in the PI3K/Akt-NF-kappaB-dependent manner. This study provides insight into MMP2/3-mediated LSCC development and lays a foundation for potential pharmacological targets to LSCC. CI - (c) 2019 Wiley Periodicals, Inc. FAU - Zhu, Yi AU - Zhu Y AUID- ORCID: 0000-0002-2222-0106 AD - Department of Radiation Oncology, Eye and ENT Hospital, Fudan University, Shanghai, China. FAU - Yan, Li AU - Yan L AD - Department of Radiation Oncology, Eye and ENT Hospital, Fudan University, Shanghai, China. FAU - Zhu, Wenjia AU - Zhu W AD - Department of Radiation Oncology, Eye and ENT Hospital, Fudan University, Shanghai, China. FAU - Song, Xinmao AU - Song X AD - Department of Radiation Oncology, Eye and ENT Hospital, Fudan University, Shanghai, China. FAU - Yang, Gang AU - Yang G AD - Department of Radiation Oncology, Eye and ENT Hospital, Fudan University, Shanghai, China. FAU - Wang, Shengzi AU - Wang S AD - Department of Radiation Oncology, Eye and ENT Hospital, Fudan University, Shanghai, China. LA - eng GR - SHDC12012317/Laryngeal Cancer Prevention and Control Project of Shanghai Shenkang/ PT - Journal Article DEP - 20190204 PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 SB - IM OTO - NOTNLM OT - PI3K/Akt-NF-kappaB pathway OT - epithelial-mesenchymal transformation OT - laryngeal squamous cell carcinoma OT - matrix metalloproteinases OT - migration EDAT- 2019/02/05 06:00 MHDA- 2019/02/05 06:01 CRDT- 2019/02/05 06:00 PHST- 2019/01/09 00:00 [revised] PHST- 2018/11/04 00:00 [received] PHST- 2019/01/18 00:00 [accepted] PHST- 2019/02/05 06:00 [pubmed] PHST- 2019/02/05 06:01 [medline] PHST- 2019/02/05 06:00 [entrez] AID - 10.1002/jcp.28242 [doi] PST - ppublish SO - J Cell Physiol. 2019 Sep;234(9):15847-15855. doi: 10.1002/jcp.28242. Epub 2019 Feb 4.