SRPX and HMCN1 regulate cancer‑associated fibroblasts to promote the invasiveness of ovarian carcinoma

Oncol Rep. 2019 Dec;42(6):2706-2715. doi: 10.3892/or.2019.7379. Epub 2019 Oct 17.


Cancer‑associated fibroblasts (CAFs) are known to be essential in cancer initiation and development. However, the role of CAFs in promoting ovarian cancer (OC) invasion remains to be fully elucidated. To address this in the present study, 49 clinical OC specimens were used to evaluate the roles of CAFs in promoting ovarian tumor migration and invasion and disease progression. It was found that the sushi repeat‑containing protein, X‑linked (SRPX) and hemicentin 1 (HMCN1) genes were significantly upregulated in CAFs from high‑grade serous carcinoma (HGSC) and clear cell carcinoma (CCC) samples, the two major histological types of OC with frequently poor patient survival rates. The short hairpin (sh)RNA‑mediated silencing of SRPX and HMCN1 in fibroblasts significantly suppressed the Transwell invasive activities of OC cells. Further experiments showed that SRPX and HMCN1 regulated the invasiveness of OC via the Ras homology family member A (RhoA) signaling pathway in fibroblasts. Therefore, the findings of the present study suggest that targeting the CAF genes, SRPX and HMCN1, can inhibit OC migration and invasion. These data highlight the importance of CAF‑OC crosstalk signaling in cancer invasion and demonstrate the potential for improved efficacy of OC treatment by targeting CAF‑SRPX/HMCN1.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Cancer-Associated Fibroblasts / metabolism
  • Cancer-Associated Fibroblasts / pathology
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoglobulins / genetics*
  • Membrane Proteins / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Signal Transduction / genetics
  • rhoA GTP-Binding Protein / genetics


  • Biomarkers, Tumor
  • HMCN1 protein, human
  • Immunoglobulins
  • Membrane Proteins
  • SRPX protein, human
  • rhoA GTP-Binding Protein