Calcium-dependent FAK/CREB/TNNC1 signalling mediates the effect of stromal MFAP5 on ovarian cancer metastatic potential. Nat Commun 2014 Oct 03;5:5092
Date
10/04/2014Pubmed ID
25277212Pubmed Central ID
PMC4185407DOI
10.1038/ncomms6092Scopus ID
2-s2.0-84920567826 (requires institutional sign-in at Scopus site) 98 CitationsAbstract
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.
Author List
Leung CS, Yeung TL, Yip KP, Pradeep S, Balasubramanian L, Liu J, Wong KK, Mangala LS, Armaiz-Pena GN, Lopez-Berestein G, Sood AK, Birrer MJ, Mok SCAuthor
Sunila Pradeep PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
ActinsAdenocarcinoma
Calcium
Cell Line, Tumor
Cell Movement
Contractile Proteins
Cyclic AMP Response Element-Binding Protein
Female
Focal Adhesion Protein-Tyrosine Kinases
Gene Expression Regulation, Neoplastic
Gene Silencing
Glycoproteins
Humans
Immunohistochemistry
Intercellular Signaling Peptides and Proteins
Neoplasm Metastasis
Ovarian Neoplasms
Prognosis
RNA, Small Interfering
Signal Transduction
Stromal Cells
Treatment Outcome
Troponin C
