Knockdown of ELMO3 Suppresses Growth, Invasion and Metastasis of Colorectal Cancer

Int J Mol Sci. 2016 Dec 16;17(12):2119. doi: 10.3390/ijms17122119.

Abstract

The engulfment and cell motility (ELMOs) family of proteins plays a crucial role in tumor cell migration and invasion. However, the function of ELMO3 is poorly defined. To elucidate its role in the development and progression of colorectal cancer (CRC), we examined the expression of ELMO3 in 45 cases of paired CRC tumor tissues and adjacent normal tissues. Furthermore, we assessed the effect of the knockdown of ELMO3 on cell proliferation, cell cycle, migration, invasion and F-actin polymerization in HCT116 cells. The result shows that the expression of ELMO3 in CRC tissues was significantly increased in comparison to the adjacent normal colorectal tissues. Moreover, this overexpression was associated with tumor size (p = 0.007), tumor differentiation (p = 0.001), depth of invasion (p = 0.009), lymph node metastasis (p = 0.003), distant metastasis (p = 0.013) and tumor, node, metastasis (TNM)-based classification (p = 0.000). In in vitro experiments, the silencing of ELMO3 inhibited cell proliferation, invasion, metastasis, and F-actin polymerization, and induced Gap 1 (G1) phase cell cycle arrest. Our study demonstrates that ELMO3 is involved in the processes of growth, invasion and metastasis of CRC, and could be used a potential molecular diagnostic tool or therapy target of CRC.

Keywords: ELMO; colorectal cancer; engulfment and cell mobility; invasion; metastasis; proliferation.

MeSH terms

  • Actins / metabolism
  • Adaptor Proteins, Signal Transducing / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Cytoskeletal Proteins / genetics*
  • Female
  • G1 Phase Cell Cycle Checkpoints / genetics*
  • HCT116 Cells
  • Humans
  • Lymphatic Metastasis / genetics
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • RNA Interference
  • RNA, Small Interfering / genetics

Substances

  • Actins
  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • ELMO3 protein, human
  • RNA, Small Interfering