Calcium Dependent FAK/CREB/TNNC1 Signaling Mediates the Effect of Stromal MFAP5 on Ovarian Cancer Metastatic Potential

Ovarian cancer is the most lethal gynaecologic malignancy in the United States, and advanced serous ovarian adenocarcinoma is responsible for most ovarian cancer deaths. However, the stroma-derived molecular determinants that modulate patient survival are yet to be characterized. Here we identify a stromal gene signature for advanced high-grade serous ovarian cancer using microdissected stromal ovarian tumour samples and find that stromal microfibrillar-associated protein 5 (MFAP5) is a prognostic marker for poor survival. Further functional studies reveal that FAK/CREB/TNNC1 signalling pathways mediate the effect of MFAP5 on ovarian cancer cell motility and invasion potential. Targeting stromal MFAP5 using MFAP5-specific siRNA encapsulated in chitosan nanoparticles significantly decreases ovarian tumour growth and metastasis in vivo, suggesting that it may be a new modality of ovarian cancer treatment. The prognostic significance of stromal cells in ovarian cancer has not been explored. Here the authors show that stromal microfibrillar-associated protein 5 (MFAP5) drives metastasis of ovarian cancer and represents a new a prognostic marker related to decreased survival.

• Publication year

  2014

• Venue

  Nature Communications

• Publication date

  2014-09-18

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/ncomms6092PMID 25277212PMCID 4185407
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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