Sex-determining region Y-related high mobility group box (SOX)-2 is overexpressed in cervical squamous cell carcinoma and contributes cervical cancer cell migration and invasion in vitro.
Sex-determining region Y-related high mobility group box 2 (SOX-2) is a key pluripotency-associated transcription factor and may be implicated in the pathogenesis of cervical squamous cell carcinoma (SCC). The aim of this study was to explore SOX-2 expression in cervical SCC tissues and to examine whether and how SOX-2 regulates the malignant behaviors of cervical SCC cells in vitro. We here found that SOX-2 expression in the examined cervical SCC tissues was higher than that in the normal cervical and cervical intraepithelial neoplasia (CIN) tissues. Higher protein level of SOX-2 (nuclear positive staining cells ≥50 %) was detected in 34.9 % (29 out of 83 cases) of cervical SCC patients. We also noted that 100 % of well-differentiated and 66.7 % of moderately differentiated cervical SCCs showed lower SOX-2 expression (nuclear positive staining cells <50 %), while 58.8 % of poorly differentiated tumors had higher SOX-2 expression (P < 0.05). Furthermore, the migratory and invasive capabilities of SiHa cervical cancer cells were enhanced when SOX-2 was upregulated whereas suppressed when SOX-2 was downregulated. Also, the phosphorylation levels of protein kinase B (Akt) and extracellular regulated protein kinases (ERK) 1/2 were increased in SOX-2-overexpressed cancer cells but decreased in SOX-2-depleted cells. Additionally, LY294002 (Akt pathway inhibitor) or U0126 (ERK pathway inhibitor) significantly suppressed SOX-2-overexpression-induced migration and invasion in SiHa cells. Our results indicate that differentially expressed SOX-2 is associated with tumor differentiation (P < 0.05) and that SOX-2 contributes to the migratory and invasive behaviors of cervical SCC in vitro.
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, People's Republic of China.
Xiaohan
X
Chang
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, People's Republic of China.
Jing
J
Zhang
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, People's Republic of China.
Chenglin
C
Huang
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, People's Republic of China.
Xiaoao
X
Pang
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, People's Republic of China.
Qingshuang
Q
Luo
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, People's Republic of China.
Huijie
H
Zhang
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, People's Republic of China. zsl0909@sina.com.
Shulan
S
Zhang
D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014945:Wound Healing; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors
Cervical squamous cell carcinoma; Clinicopathologic features; Invasion; Migration; Sex-determining region Y-related high mobility group box 2