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

被引：104

作者：

Leung, Cecilia S. ^{[1
,2
]}

Yeung, Tsz-Lun ^{[1
]}

Yip, Kay-Pong ^{[3
]}

Pradeep, Sunila ^{[1
]}

Balasubramanian, Lavanya ^{[3
]}

Liu, Jinsong ^{[4
]}

Wong, Kwong-Kwok ^{[1
,2
]}

Mangala, Lingegowda S. ^{[1
,5
]}

Armaiz-Pena, Guillermo N. ^{[1
]}

Lopez-Berestein, Gabriel ^{[5
,6
,7
]}

Sood, Anil K. ^{[1
,2
,5
,6
]}

Birrer, Michael J. ^{[8
]}

Mok, Samuel C. ^{[1
,2
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA

[2] Univ Texas Houston, Grad Sch Biomed Sci, Houston, TX 77030 USA

[3] Univ S Florida, Dept Mol Pharmacol & Physiol, Tampa, FL 33612 USA

[4] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA

[5] Univ Texas MD Anderson Canc Ctr, Ctr RNA Interference & Noncoding RNAs, Houston, TX 77030 USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA

[8] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA

来源：

NATURE COMMUNICATIONS | 2014年 / 5卷

基金：

美国国家卫生研究院;

关键词：

TUMOR ANGIOGENESIS; GENE-EXPRESSION; PKC-THETA; ACTIVATION; FIBROBLASTS; SIGNATURE; PATTERNS; SURVIVAL; KINASE; PHOSPHORYLATION;

D O I：

10.1038/ncomms6092

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：15

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