Elmo1 Helps Dock180 to Regulate Rac1 Activity and Cell Migration of Ovarian Cancer

Wang, Jin MD*; Dai, Jie-min MD*; Che, Ya-ling MD*; Gao, Yi-meng MD*; Peng, Hui-juan MD*; Liu, Bin MD, PhD; Wang, Hui MD, PhD*; Linghu, Hua MD, PhD*

International Journal of Gynecological Cancer:
doi: 10.1097/IGC.0000000000000137
Basic Science
Abstract

Objective: Engulfment and cell motility 1 (Elmo1) has been reported to cooperate with dedicator of cytokinesis 1 (Dock180) and to be linked to the invasive phenotype of cancer cells through activating small G-protein Rac. We aimed to study the role of Elmo1 in the malignant migration of ovarian cancer.

Methods: Engulfment and cell motility 1 expression was evaluated in specimens from 93 patients with serous ovarian cancer (SOC) by immunohistochemical staining. Next, Elmo1-RNAi cells were established by validated small interference RNAs. Cell proliferation and cell motility were observed and compared with Dock180-RNAi cells. To confirm their synergetic contribution to forming focal adhesion and activating Rac1, Rac1-GTP level was measured by GST pull-down assay and immunofluorescence was used to observe focal adhesion formation both in Elmo1-RNAi and Dock180-RNAi cells.

Results: Engulfment and cell motility 1 was mainly overexpressed in high-grade SOC tissues. Western blot analysis demonstrated that both Elmo1 and Dock180 expressions were hampered in Elmo1-RNAi cells. Compared with the negative control, decreased colony formation and cell invasion were observed in Elmo1-RNAi cells and Dock180-RNAi cells. Consistently, both exhibited reduced Rac1-GTP level and inhibited focal adhesion formation.

Conclusions: Engulfment and cell motility 1 presents with synergetic action in helping Dock180 to activate Rac1 and promote cell motility, and thus promote untoward expansion and aggressiveness of SOC.

Author Information

*Department of Obstetrics and Gynecology, First Affiliated Hospital of Chongqing Medical University; and †Department of Pathology, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing, People’s Republic of China.

Address correspondence and reprint requests to Hua Linghu, MD, PhD, Department of Obstetrics and Gynecology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China. E-mail: linghu_hua@yahoo.com.

Supported by grants from the National Natural Science Foundation of China (NSFC nos. 81072120 and C30772330) and medical scientific research project (key project) from Chongqing Health Bureau (2012-1-007).

Jin Wang is now with the Department of Obstetrics and Gynecology, Banan District People’s Hospital, Chongqing, China.

Jin Wang and Jie-min Dai contributed equally to this work.

The authors declare no conflicts of interest.

Received January 14, 2014

Accepted March 2, 2014

© 2014 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology.