Overexpression of SOX2 promotes migration, invasion, and epithelial-mesenchymal transition through the Wnt/β-catenin pathway in laryngeal cancer Hep-2 cells.
SOX2 is a high-mobility group box containing transcription factor essential for the maintenance of embryonic stem cells. Recent evidence indicates that SOX2 overexpression correlates with metastasis and poor prognosis in patients with laryngeal squamous cell cancer. To investigate how SOX2 contributes to this aggressive phenotype, we introduced the human SOX2 gene into a low SOX2-expressing human laryngeal cancer cell line Hep-2. Cell migration and invasion were determined by the Transwell assay with or without Matrigel coating. The epithelial-mesenchymal transition (EMT)-related markers were assayed by Western blot analysis or immunofluorescence. Our results showed that exogenous expression of SOX2 in Hep-2 cells substantially promoted their migratory and invasive capabilities in culture. Moreover, Hep-2 cells stably overexpressing SOX2 underwent EMT phenotype, as evidenced by mesenchymal morphology, decreased expression of epithelial marker (E-cadherin), and increased expression of mesenchymal markers (N-cadherin, vimentin, fibronectin, and α-smooth muscle actin). Strikingly, Western blot analysis and immunofluorescence also showed that overexpression of SOX2 resulted in substantial increase and nuclear accumulation of β-catenin in Hep-2 cells. However, small interfering RNA targeting β-catenin significantly attenuated the reduced expression of E-cadherin and increased cell migration and invasion abilities in SOX2-overexpressing cells, suggesting that SOX2-induced EMT process, migration, and invasion are dependent on β-catenin activation. Taken together, our findings underscore a novel role for SOX2 in laryngeal cancer migration and invasion.
Department of Otorhinolaryngology, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, Liaoning, People's Republic of China, cmu1hyangning@163.com.
Ning
N
Yang
Lian
L
Hui
Yan
Y
Wang
Huijun
H
Yang
Xuejun
X
Jiang
D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D007822:Laryngeal Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D055748:SOXB1 Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology*
C495270:CTNNB1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D051176:beta Catenin