Calcium-dependent FAK/CREB/TNNC1 signalling mediates the effect of stromal MFAP5 on ovarian cancer metastatic potential.

Cecilia S Leung, Tsz-Lun Yeung, Kay-Pong Yip, Sunila Pradeep, Lavanya Balasubramanian, Jinsong Liu, Kwong-Kwok Wong, Lingegowda S Mangala, Guillermo N Armaiz-Pena, Gabriel Lopez-Berestein, Anil K Sood, Michael J Birrer, Samuel C Mok

Index: Nat. Commun. 5 , 5092, (2014)

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Abstract

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.