Elmo1 helps dock180 to regulate Rac1 activity and cell migration of ovarian cancer.

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.

• Authors: Jin Wang, Jie-min Dai, Ya-ling Che, Yi-meng Gao, Hui-juan Peng, Bin Liu, Hui Wang, Hua Linghu
• Journal: International journal of gynecological cancer : official journal of the International Gynecological Cancer Society (Int J Gynecol Cancer) Vol. 24 Issue 5 Pg. 844-50 (Jun 2014) ISSN: 1525-1438 [Electronic] England
• PMID: 24819662 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• DOCK1 protein, human
• ELMO1 protein, human
• RAC1 protein, human
• RNA, Small Interfering
• Guanosine Triphosphate
• rac GTP-Binding Proteins
• rac1 GTP-Binding Protein

Topics

• Adaptor Proteins, Signal Transducing (antagonists & inhibitors, genetics, metabolism)
• Adult
• Aged
• Aged, 80 and over
• Blotting, Western
• Cell Adhesion
• Cell Cycle
• Cell Movement
• Cell Proliferation
• Cystadenocarcinoma, Serous (metabolism, pathology)
• Female
• Flow Cytometry
• Fluorescent Antibody Technique
• Gene Expression Regulation, Neoplastic
• Guanosine Triphosphate (metabolism)
• Humans
• Immunoenzyme Techniques
• Middle Aged
• Neoplasm Grading
• Ovarian Neoplasms (metabolism, pathology)
• Prognosis
• RNA, Small Interfering (genetics)
• Tumor Cells, Cultured
• rac GTP-Binding Proteins (antagonists & inhibitors, genetics, metabolism)
• rac1 GTP-Binding Protein (metabolism)