SOX2 promotes the migration and invasion of laryngeal cancer cells by induction of MMP-2 via the PI3K/Akt/mTOR pathway.
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.
Department of Otorhinolaryngology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P.R. China.
Ning
N
Yang
Department of Otorhinolaryngology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P.R. China.
Lian
L
Hui
Department of Otorhinolaryngology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P.R. China.
Yan
Y
Wang
Department of Otorhinolaryngology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P.R. China.
Huijun
H
Yang
Department of Otorhinolaryngology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P.R. China.
Xuejun
X
Jiang
D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness / Q000235:genetics; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
D020778:Matrix Metalloproteinase 2; D061965:Matrix Metalloproteinase Inhibitors; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D055748:SOXB1 Transcription Factors; D058570:TOR Serine-Threonine Kinases; C527782:SOX2 protein, human; C546842:MTOR protein, human