Increased expression of GEF-H1 promotes colon cancer progression by RhoA signaling

Pathol Res Pract. 2019 May;215(5):1012-1019. doi: 10.1016/j.prp.2019.02.008. Epub 2019 Feb 27.


Colorectal cancer (CRC) is the third most common malignancy and a leading cause of cancer-related death worldwide. GEF-H1 is considered a RhoA-specific guanine nucleotide exchange factor. GEF-H1 upregulation may contribute to cancer cell migration and invasion and tumor progression. However, the expression and role of GEF-H1 in CRC have not yet been elucidated. This study attempted to elucidate how GEF-H1 drives tumor formation, motility, invasion and metastasis in colon cancer (CC). The expression of GEF-H1 in CC tissue microarrays (TMAs) was analyzed by immunohistochemistry (IHC). GEF-H1 was upregulated in CC tissues compared with adjacent non-tumoral tissues. In addition, we found that high GEF-H1 expression correlated with shorter overall survival and distant metastasis. Migration and invasion assays showed that GEF-H1 upregulation increased CC cell motility, invasion and metastasis. In contrast, functional knockdown of GEF-H1 by RNAi rescued the effects caused by GEF-H1 overexpression in CC cells. Overexpression of GEF-H1 re-organized the actin cytoskeleton, with increased punctate paxillin staining and F-actin stress fibers. Furthermore, western blotting showed that RhoA activation triggered by GEF-H1 overexpression caused phosphorylation of its downstream target, MLC2, in CC cells. In summary, the present study revealed that GEF-H1 is upregulated in CC tissues and plays a key role in CC metastasis through the GEF-H1-RhoA-MLC2 signaling pathway.

Keywords: Colon carcinoma; Cytoskeleton rearrangements; GEF-H1; RhoA.

MeSH terms

  • Adult
  • Aged
  • Cell Movement / physiology
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology*
  • Disease Progression
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Rho Guanine Nucleotide Exchange Factors / metabolism*
  • Signal Transduction / physiology
  • Up-Regulation
  • rhoA GTP-Binding Protein / metabolism*


  • ARHGEF2 protein, human
  • Rho Guanine Nucleotide Exchange Factors
  • RHOA protein, human
  • rhoA GTP-Binding Protein