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Rac1 expression in epithelial ovarian cancer: effect on cell EMT and clinical outcome

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Abstract

Ras-related C3 botulinum toxin substrate 1 (rac1) has been implicated in tumor epithelial–mesenchymal transition (EMT); however, limited information is available regarding the role of rac1 in epithelial ovarian cancer (EOC). This study aimed to evaluate the correlation of rac1 expression with EMT and EOC prognosis. Rac1 protein levels of 150 EOC specimens were evaluated by immunohistochemical staining. Survival analysis was performed to determine the correlation between rac1 expression and survival. Cellular and molecular changes were also examined after rac1 in ovarian cancer cells was silenced in vitro and in vivo. The mechanism of rac1 on EMT was investigated by Western blot analysis. Rac1 was highly expressed in EOC. Rac1 overexpression was closely associated with advanced stage based on International Federation of Gynecology and Obstetrics, poor grade, serum Ca-125, and residual tumor size. Survival analyses demonstrated that patients with high rac1 expression levels were more susceptible to early tumor recurrence with very poor prognosis. This study revealed that rac1 downregulation decreased cell EMT and proliferation capability in vitro and in vivo. Rac1 expression possibly altered cell EMT by interacting with p21-activated kinase 1 and p38 mitogen-activated protein kinase signaling pathways. The present study showed that rac1 overexpression is associated with cell EMT and poor EOC prognosis. Rac1 possibly plays an important role in predicting EOC metastasis.

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Acknowledgments

The authors thank Lixue Chen and Weixue Tang for their support and technical assistance. The authors also thank Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, for providing the experimental materials. This study was supported by the National Natural Science Foundation of China (Grant No. 81372800/H1621) and Superior Doctoral Academic Dissertations Research Grant from the Chongqing Medical University.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China

    Ruobing Leng, Haixia Wang, Jun Kuang & Liangdan Tang

  2. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Gang Liao

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  1. Ruobing Leng
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Correspondence to Liangdan Tang.

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Leng, R., Liao, G., Wang, H. et al. Rac1 expression in epithelial ovarian cancer: effect on cell EMT and clinical outcome. Med Oncol 32, 28 (2015). https://doi.org/10.1007/s12032-014-0329-5

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