Department of Experimental Research, State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University; Department of Gynecologic Oncology, the Third Affiliated Hospital of Kunming Medical College (Yunnan Tumor Hospital), Kunming, China.
Department of Experimental Research, State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University.
Ann Oncol. 2012 Mar;23(3):638-646. doi: 10.1093/annonc/mdr290. Epub 2011 Jun 23.
This study was aimed at investigating the role and molecular mechanism of Sam68 in cervical cancer lymph node metastasis.
Sam68 expression profile was detected by quantitative polymerase chain reaction, western blotting and immunohistochemical staining. Short hairpin RNA interfering approach was employed to suppress endogenous Sam68 expression in cervical cancer cells to determine its role in metastasis and the possible mechanism.
Sam68 expression in cervical cancer was significantly up-regulated at both messenger RNA and protein levels compared with that in normal cervical tissues. The high expression level of Sam68 and its cytoplasmic localization were significantly associated with risk factors including pelvic lymph node metastasis (P < 0.001), and served as independent prognostic factors for predicting shortening of the overall survival time and disease-free survival time in patients with early-stage cervical cancer. Moreover, down-regulation of Sam68 in cervical cancer cells remarkably inhibited cellular motility and invasion. In addition, down-regulation of Sam68 reversed epithelial-mesenchymal transition through inhibiting the Akt/ GSK-3β/Snail pathway.
This study demonstrated that Sam68 could induce cervical cancer lymph node metastasis through regulating epithelial-mesenchymal transition, and Sam68 expression profile possessed the potential to serve as predictors of pelvic lymph node metastasis in cervical cancer patients.
本研究旨在探讨 Sam68 在宫颈癌淋巴结转移中的作用及其分子机制。
采用定量聚合酶链反应、Western blot 和免疫组织化学染色检测 Sam68 的表达谱。采用短发夹 RNA 干扰方法抑制宫颈癌细胞中内源性 Sam68 的表达,以确定其在转移中的作用及其可能的机制。
与正常宫颈组织相比,宫颈癌中 Sam68 的信使 RNA 和蛋白水平均显著上调。Sam68 的高表达水平及其细胞质定位与包括盆腔淋巴结转移在内的危险因素显著相关,并且是预测早期宫颈癌患者总生存时间和无病生存时间缩短的独立预后因素。此外,下调宫颈癌细胞中的 Sam68 可显著抑制细胞迁移和侵袭。此外,下调 Sam68 通过抑制 Akt/GSK-3β/Snail 通路逆转上皮-间充质转化。
本研究表明,Sam68 可通过调节上皮-间充质转化诱导宫颈癌淋巴结转移,Sam68 的表达谱有可能成为宫颈癌患者盆腔淋巴结转移的预测因子。