PMID- 24700142 OWN - NLM STAT- MEDLINE DCOM- 20141217 LR - 20211203 IS - 1791-2431 (Electronic) IS - 1021-335X (Linking) VI - 31 IP - 6 DP - 2014 Jun TI - SOX2 promotes the migration and invasion of laryngeal cancer cells by induction of MMP-2 via the PI3K/Akt/mTOR pathway. PG - 2651-9 LID - 10.3892/or.2014.3120 [doi] AB - SOX2 is a high mobility group box containing transcription factor that has been reported to be aberrantly overexpressed in various human malignancies, including laryngeal squamous cell carcinoma (LSCC). However, the potential role of SOX2 in LSCC migration and invasion remains to be elucidated. In the present study, we generated stable transformants of human LSCC cells constitutively overexpressing SOX2 and investigated the effects of SOX2 overexpression on migration and invasion in LSCC cells as well as the possible underlying mechanisms. We found that ectopic overexpression of SOX2 in LSCC cells enhanced their migratory and invasive ability in vitro, accompanied by increased expression and activity of matrix metalloproteinase (MMP)-2. Meanwhile, SOX2-induced cell migration and invasion were significantly abrogated by a neutralizing anti-MMP-2 antibody or small interfering RNA targeting MMP-2. Furthermore, overexpression of SOX2 induced phosphorylation of Akt and mammalian target of rapamycin (mTOR), which are downstream effectors of the PI3K pathway. Finally, LY294002, an inhibitor of PI3K, also markedly abolished SOX2-induced activation of the Akt/mTOR pathway and increased cell invasion and MMP-2 expression. Taken together, we conclude that SOX2 promotes migration and invasion of laryngeal cancer cells by inducing MMP-2 via the PI3K/Akt/mTOR pathway. Our findings suggest that SOX2 may serve as a potential therapeutic target for LSCC. FAU - Yang, Ning AU - Yang N AD - Department of Otorhinolaryngology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P.R. China. FAU - Hui, Lian AU - Hui L AD - Department of Otorhinolaryngology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P.R. China. FAU - Wang, Yan AU - Wang Y AD - Department of Otorhinolaryngology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P.R. China. FAU - Yang, Huijun AU - Yang H AD - Department of Otorhinolaryngology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P.R. China. FAU - Jiang, Xuejun AU - Jiang X AD - Department of Otorhinolaryngology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P.R. China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140402 PL - Greece TA - Oncol Rep JT - Oncology reports JID - 9422756 RN - 0 (Matrix Metalloproteinase Inhibitors) RN - 0 (SOX2 protein, human) RN - 0 (SOXB1 Transcription Factors) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (Oncogene Protein v-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) SB - IM MH - Cell Movement/*genetics MH - Cell Proliferation/genetics MH - Gene Expression Regulation, Neoplastic MH - Hep G2 Cells MH - Humans MH - Laryngeal Neoplasms/*genetics/pathology MH - Matrix Metalloproteinase 2/*genetics/metabolism MH - Matrix Metalloproteinase Inhibitors MH - Neoplasm Invasiveness/genetics MH - Oncogene Protein v-akt/genetics/metabolism MH - Phosphatidylinositol 3-Kinases/genetics/metabolism MH - SOXB1 Transcription Factors/*biosynthesis/genetics MH - TOR Serine-Threonine Kinases/genetics/metabolism EDAT- 2014/04/05 06:00 MHDA- 2014/12/18 06:00 CRDT- 2014/04/05 06:00 PHST- 2014/02/14 00:00 [received] PHST- 2014/03/12 00:00 [accepted] PHST- 2014/04/05 06:00 [entrez] PHST- 2014/04/05 06:00 [pubmed] PHST- 2014/12/18 06:00 [medline] AID - 10.3892/or.2014.3120 [doi] PST - ppublish SO - Oncol Rep. 2014 Jun;31(6):2651-9. doi: 10.3892/or.2014.3120. Epub 2014 Apr 2.