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

Author

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  • Cecilia S. Leung

    (The University of Texas MD Anderson Cancer Center
    The University of Texas Graduate School of Biomedical Sciences at Houston)

  • 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
    The University of Texas Graduate School of Biomedical Sciences at Houston)

  • Lingegowda S. Mangala

    (The University of Texas MD Anderson Cancer Center
    The Center for RNA Interference and Non-Coding RNAs, 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
    The University of Texas MD Anderson Cancer Center
    The University of Texas MD Anderson Cancer Center)

  • Anil K. Sood

    (The University of Texas MD Anderson Cancer Center
    The University of Texas Graduate School of Biomedical Sciences at Houston
    The Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center
    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
    The University of Texas Graduate School of Biomedical Sciences at Houston)

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.

Suggested Citation

  • 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 , 2014. "Calcium-dependent FAK/CREB/TNNC1 signalling mediates the effect of stromal MFAP5 on ovarian cancer metastatic potential," Nature Communications, Nature, vol. 5(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6092
    DOI: 10.1038/ncomms6092
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