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 () and Samuel C. Mok ()
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Cecilia S. Leung: The University of Texas MD Anderson Cancer Center
Tsz-Lun Yeung: The University of Texas MD Anderson Cancer Center
Kay-Pong Yip: University of South Florida
Sunila Pradeep: The University of Texas MD Anderson Cancer Center
Lavanya Balasubramanian: University of South Florida
Jinsong Liu: The University of Texas MD Anderson Cancer Center
Kwong-Kwok Wong: The University of Texas MD Anderson Cancer Center
Lingegowda S. Mangala: The University of Texas MD Anderson Cancer Center
Guillermo N. Armaiz-Pena: The University of Texas MD Anderson Cancer Center
Gabriel Lopez-Berestein: The Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center
Anil K. Sood: The University of Texas MD Anderson Cancer Center
Michael J. Birrer: Massachusetts General Hospital, Harvard Medical School
Samuel C. Mok: The University of Texas MD Anderson Cancer Center

Nature Communications, 2014, vol. 5, issue 1, 1-15

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms6092

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