Calcium-dependent FAK/CREB/TNNC1 signalling mediates the effect of stromal MFAP5 on ovarian cancer metastatic potential
Copyright policy )Calcium-dependent FAK/CREB/TNNC1 signalling 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.
- Massachusetts General Hospital United States
- University of Florida United States
- Harvard University United States
- MASSACHUSETTS GENERAL HOSPITAL
- Florida Southern College United States
610, Adenocarcinoma, Article, 618, Contractile Proteins, Cell Movement, Cell Line, Tumor, Humans, Gene Silencing, Neoplasm Metastasis, RNA, Small Interfering, Cyclic AMP Response Element-Binding Protein, Glycoproteins, Ovarian Neoplasms, Prognosis, Immunohistochemistry, Actins, Gene Expression Regulation, Neoplastic, Focal Adhesion Protein-Tyrosine Kinases, Intercellular Signaling Peptides and Proteins, Calcium, Female, Signal Transduction
610, Adenocarcinoma, Article, 618, Contractile Proteins, Cell Movement, Cell Line, Tumor, Humans, Gene Silencing, Neoplasm Metastasis, RNA, Small Interfering, Cyclic AMP Response Element-Binding Protein, Glycoproteins, Ovarian Neoplasms, Prognosis, Immunohistochemistry, Actins, Gene Expression Regulation, Neoplastic, Focal Adhesion Protein-Tyrosine Kinases, Intercellular Signaling Peptides and Proteins, Calcium, Female, Signal Transduction
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