title: High-mobility group box 1 is overexpressed in cervical carcinoma and promotes cell invasion and migration in vitro.
abstract: The present study aimed to investigate the expression of high-mobility group box 1 protein (HMGB1) in cervical carcinoma and explore whether or not HMGB1 promotes cervical carcinoma cell invasion and migration in vitro and the related mechanism. HMGB1, nuclear factor-κB (NF-κB), E-cadherin and N-cadherin protein expression was analyzed in tissues from 48 cervical carcinomas, 51 cervical intraepithelial neoplasia (CIN) and tissues from 24 healthy controls using immunohistochemistry. HeLa cells were treated with different concentrations of HMGB1 (0, 10, 100, and 1,000 ng/ml) at different time-points (0, 24, 48 and 72 h), and changes in cell morphology and biological behaviors were observed. Changes in the expression levels of E-cadherin, N-cadherin, NF-κB and the inhibitor κB (IκB) in the treated cells were detected by western blot analysis and real-time PCR. HMGB1 expression exhibited a gradually increasing trend in the normal cervical tissues, CIN and cervical cancer, and there was statistical significance between the three groups (P<0.05). HMGB1 expression level was associated with FIGO stage, lymph node metastasis and differentiation (P<0.05). HMGB1 expression was positively related to N-cadherin and NF-κB; and HMGB1 had a negative relationship with E-cadherin. HMGB1 stimulation caused HeLa cells to lose cell polarity and transition from epithelial cells into spindle-shaped cells with sparse cell-cell junctions. The expression levels of E-cadherin and IκB in the cytoplasm were reduced, while N-cadherin expression was increased. The level of NF-κB expression in the nucleus was also increased. Treatment with NF-κB inhibitor (BAY11-7082) and receptor for advanced glycation end products (RAGE) antagonist (anti-RAGE) significantly suppressed HMGB1‑mediated epithelial-to-mesenchymal transition in the HeLa cervical cancer cells. The results suggest that HMGB1 is associated with outcomes of cervical cancer and promotes subsequent invasion and metastasis of cervical cancer cells by activating the NF-κB signaling pathway. This potential mechanism could be an important determinant of cervical cancer metastasis.
authors.affiliation: Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Heping, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Xiaoao
authors.initials: X
authors.lastname: Pang
authors.affiliation: Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Heping, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Heping, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Shulan
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000378:metabolism / Q000556:secondary*
chemical_list: D014408:Biomarkers, Tumor; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D012333:RNA, Messenger