Calcium dependent FAK/CREB/TNNC1 signaling 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

doi:10.1038/ncomms6092

Calcium dependent FAK/CREB/TNNC1 signaling 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

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98 Scopus citations

Abstract

Ovarian cancer is the most lethal gynecologic 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 have yet to be characterized. Here we identify a stromal gene signature for advanced high-grade serous ovarian cancer using microdissected stromal ovarian tumor 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 signaling 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 tumor growth and metastasis in vivo, suggesting that it may be a new modality of ovarian cancer treatment.

Original language	English (US)
Article number	5092
Journal	Nature communications
Volume	5
DOIs	https://doi.org/10.1038/ncomms6092
State	Published - 2014

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

MD Anderson CCSG core facilities

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10.1038/ncomms6092

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Leung, C. S., Yeung, T. L., Yip, K. P., Pradeep, S., Balasubramanian, L., Liu, J., Wong, K. K., Mangala, L. S., Armaiz-Pena, G. N., Lopez-Berestein, G., Sood, A. K., Birrer, M. J., & Mok, S. C. (2014). Calcium dependent FAK/CREB/TNNC1 signaling mediates the effect of stromal MFAP5 on ovarian cancer metastatic potential. Nature communications, 5, Article 5092. https://doi.org/10.1038/ncomms6092

@article{ec1551a46f9947ff8bd4796fcfccdc02,

title = "Calcium dependent FAK/CREB/TNNC1 signaling mediates the effect of stromal MFAP5 on ovarian cancer metastatic potential",

abstract = "Ovarian cancer is the most lethal gynecologic 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 have yet to be characterized. Here we identify a stromal gene signature for advanced high-grade serous ovarian cancer using microdissected stromal ovarian tumor 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 signaling 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 tumor growth and metastasis in vivo, suggesting that it may be a new modality of ovarian cancer treatment.",

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

note = "Funding Information: This study was supported in part by grants RO1CA133057, RO1CA142832, RC4CA156551, U54CA151668, UH2 TR000943, MD Anderson Ovarian Cancer SPORE grant P50CA083639 and MD Anderson Cancer Center Support Grant CA016672 from the National Institutes of Health; the US Department of Health and Human Services; the Gilder Foundation; grant RP100094 from the Cancer Prevention Research Institute of Texas; and funding from the Mary L. Chapman Foundation.",

year = "2014",

doi = "10.1038/ncomms6092",

language = "English (US)",

volume = "5",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

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TY - JOUR

T1 - Calcium dependent FAK/CREB/TNNC1 signaling mediates the effect of stromal MFAP5 on ovarian cancer metastatic potential

AU - Leung, Cecilia S.

AU - Yeung, Tsz Lun

AU - Yip, Kay Pong

AU - Pradeep, Sunila

AU - Balasubramanian, Lavanya

AU - Liu, Jinsong

AU - Wong, Kwong Kwok

AU - Mangala, Lingegowda S.

AU - Armaiz-Pena, Guillermo N.

AU - Lopez-Berestein, Gabriel

AU - Sood, Anil K.

AU - Birrer, Michael J.

AU - Mok, Samuel C.

N1 - Funding Information: This study was supported in part by grants RO1CA133057, RO1CA142832, RC4CA156551, U54CA151668, UH2 TR000943, MD Anderson Ovarian Cancer SPORE grant P50CA083639 and MD Anderson Cancer Center Support Grant CA016672 from the National Institutes of Health; the US Department of Health and Human Services; the Gilder Foundation; grant RP100094 from the Cancer Prevention Research Institute of Texas; and funding from the Mary L. Chapman Foundation.

PY - 2014

Y1 - 2014

N2 - Ovarian cancer is the most lethal gynecologic 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 have yet to be characterized. Here we identify a stromal gene signature for advanced high-grade serous ovarian cancer using microdissected stromal ovarian tumor 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 signaling 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 tumor growth and metastasis in vivo, suggesting that it may be a new modality of ovarian cancer treatment.

AB - Ovarian cancer is the most lethal gynecologic 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 have yet to be characterized. Here we identify a stromal gene signature for advanced high-grade serous ovarian cancer using microdissected stromal ovarian tumor 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 signaling 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 tumor growth and metastasis in vivo, suggesting that it may be a new modality of ovarian cancer treatment.

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

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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