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

Int J Gynecol Cancer. 2014 Jun;24(5):844-50. doi: 10.1097/IGC.0000000000000137.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • 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