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Rac GTP酶激活蛋白1促进上皮性卵巢癌的致癌进程。

Rac GTPase activating protein 1 promotes oncogenic progression of epithelial ovarian cancer.

作者信息

Wang Chuanjiang, Wang Wenxia, Liu Yujuan, Yong Min, Yang Yamei, Zhou Honggui

机构信息

Department of Reproductive Center, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.

Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, China.

出版信息

Cancer Sci. 2018 Jan;109(1):84-93. doi: 10.1111/cas.13434. Epub 2017 Nov 22.

Abstract

Rac GTPase activating protein 1 (RacGAP1) can regulate cytokinesis and cell differentiation. The oncogenic role of RacGAP1 has been partially studied in gastric cancer, colorectal cancer, and breast cancer. In the present study, we endeavor to evaluate its expression and functions in epithelial ovarian cancer (EOC). We retrospectively collected the clinicopathological information of 117 patients who underwent curative surgery for EOC. Expression of RacGAP1 protein in primary tumor tissues was evaluated by immunohistochemistry, which was significantly associated with tumor pathological grade, tumor stage, and lymph node metastasis. Patients with lower RacGAP1 level had a longer survival time and lower recurrence risk. Multivariate results identified the independent prognostic role of RacGAP1 for both recurrence and survival in EOC patients. Cellular studies showed that RacGAP1 can positively regulate the activation of RhoA and Erk proteins. In addition, wound healing assay and Transwell assay found that RacGAP1 can up-regulate the migration and invasion process of EOC cells, respectively. In all, our results not only confirmed the prognostic role of RacGAP1 for recurrence and survival in EOC patients, but also highlighted its possible potency for drug development.

摘要

Rac小GTP酶激活蛋白1(RacGAP1)可调节胞质分裂和细胞分化。RacGAP1在胃癌、结直肠癌和乳腺癌中的致癌作用已得到部分研究。在本研究中,我们致力于评估其在上皮性卵巢癌(EOC)中的表达及功能。我们回顾性收集了117例行EOC根治性手术患者的临床病理信息。采用免疫组织化学法评估原发性肿瘤组织中RacGAP1蛋白的表达,其与肿瘤病理分级、肿瘤分期及淋巴结转移显著相关。RacGAP1水平较低的患者生存时间更长,复发风险更低。多因素分析结果确定了RacGAP1对EOC患者复发和生存的独立预后作用。细胞研究表明,RacGAP1可正向调节RhoA和Erk蛋白的激活。此外,伤口愈合实验和Transwell实验发现,RacGAP1可分别上调EOC细胞的迁移和侵袭过程。总之,我们的结果不仅证实了RacGAP1对EOC患者复发和生存的预后作用,还突出了其在药物研发方面的潜在潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff9f/5765294/6426f9864614/CAS-109-84-g001.jpg

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