Resveratrol suppresses breast cancer cell invasion by inactivating a RhoA/YAP signaling axis

被引：52

作者：

Kim, Yu Na ^{[1
]}

Choe, So Ra ^{[1
]}

Cho, Kyung Hwa ^{[1
]}

Cho, Do Yeun ^{[2
]}

Kang, Jaeku ^{[1
]}

Park, Chang Gyo ^{[1
]}

Lee, Hoi Young ^{[1
]}

机构：

[1] Konyang Univ, Dept Pharmacol, Coll Med, 821 Med Sci Bldg,158 Gwanjeodong Ro, Daejeon 35365, South Korea

[2] Konyang Univ, Dept Hematol & Oncol, Coll Med, Daejeon, South Korea

来源：

EXPERIMENTAL AND MOLECULAR MEDICINE | 2017年 / 49卷

基金：

新加坡国家研究基金会;

关键词：

PROTEOLYTIC-ENZYME EXPRESSION; HIPPO PATHWAY; SIZE-CONTROL; YAP; APOPTOSIS; GROWTH; LPA; INHIBITION; MIGRATION; TAZ;

D O I：

10.1038/emm.2016.151

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Hippo/YAP signaling is implicated in tumorigenesis and progression of various cancers. By inhibiting a plethora signaling cascades, resveratrol has strong anti-tumorigenic and anti-metastatic activity. In the present study, we demonstrate that resveratrol decreases the expression of YAP target genes. In addition, our data showed that resveratrol attenuates breast cancer cell invasion through the activation of Lats1 and consequent inactivation of YAP. Strikingly, we also demonstrate that resveratrol inactivates RhoA, leading to the activation of Lats1 and induction of YAP phosphorylation. Further, resveratrol in combination with other agents that inactivate RhoA or YAP showed more marked suppression of breast cancer cell invasion compared with single treatment. Collectively, these findings indicate the beneficial effects of resveratrol on breast cancer patients by suppressing the RhoA/Lats1/YAP signaling axis and subsequently inhibiting breast cancer cell invasion.

引用

页码：e296 / e296

页数：9

共 48 条

[1] Resveratrol and estradiol exert disparate effects on cell migration, cell surface actin structures, and focal adhesion assembly in MDA-MB-231 human breast cancer [J].

Azios, NG ;

Dharmawardhane, SF .

NEOPLASIA, 2005, 7 (02) :128-140

[2] Estrogen and resveratrol regulate rac and cdc42 signaling to the actin cytoskeleton of metastatic breast cancer cells [J].

Azios, Nicolas G. ;

Krishnamoorthyy, Lakshmi ;

Harris, Micheleen ;

Cubano, Luis A. ;

Cammer, Michael ;

Dharmawardhane, Surangani F. .

NEOPLASIA, 2007, 9 (02) :147-158

[3] Plant foods and herbal sources of resveratrol [J].

Burns, J ;

Yokota, T ;

Ashihara, H ;

Lean, MEJ ;

Crozier, A .

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2002, 50 (11) :3337-3340

[4] The role of LPA and YAP signaling in long-term migration of human ovarian cancer cells [J].

Cai, Hui ;

Xu, Yan .

CELL COMMUNICATION AND SIGNALING, 2013, 11

[5] Resveratrol, a natural product present in wine, decreases tumour growth in a rat tumour model [J].

Carbó, N ;

Costelli, P ;

Baccino, FM ;

López-Soriano, FJ ;

Argilés, JM .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 254 (03) :739-743

[6] Anti-proliferative and gene expression actions of resveratrol in breast cancer cells in vitro [J].

Chin, Yu-Tang ;

Hsieh, Meng-Ti ;

Yang, Sheng-Huei ;

Tsai, Po-Wei ;

Wang, Shwu-Huey ;

Wang, Ching-Chiung ;

Lee, Yee-Shin ;

Cheng, Guei-Yun ;

HuangFu, Wei-Chun ;

London, David ;

Tang, Heng-Yuan ;

Fu, Earl ;

Yen, Yun ;

Liu, Leroy F. ;

Lin, Hung-Yun ;

Davis, Paul J. .

ONCOTARGET, 2014, 5 (24) :12891-12907

[7] hTERT mediates norepinephrine-induced Slug expression and ovarian cancer aggressiveness [J].

Choi, M. J. ;

Cho, K. H. ;

Lee, S. ;

Bae, Y. J. ;

Jeong, K. J. ;

Rha, S. Y. ;

Choi, E. J. ;

Park, J. H. ;

Kim, J. M. ;

Lee, J-S ;

Mills, G. B. ;

Lee, H. Y. .

ONCOGENE, 2015, 34 (26) :3402-3412

[8]

Clément MV, 1998, BLOOD, V92, P996

[9] The Hippo Transducer TAZ Confers Cancer Stem Cell-Related Traits on Breast Cancer Cells [J].

Cordenonsi, Michelangelo ;

Zanconato, Francesca ;

Azzolin, Luca ;

Forcato, Mattia ;

Rosato, Antonio ;

Frasson, Chiara ;

Inui, Masafumi ;

Montagner, Marco ;

Parenti, Anna R. ;

Poletti, Alessandro ;

Daidone, Maria Grazia ;

Dupont, Sirio ;

Basso, Giuseppe ;

Bicciato, Silvio ;

Piccolo, Stefano .

CELL, 2011, 147 (04) :759-772

[10] Cerivastatin, an inhibitor of HMG-CoA reductase, inhibits the signaling pathways involved in the invasiveness and metastatic properties of highly invasive breast cancer cell lines:: an in vitro study [J].

Denoyelle, C ;

Vasse, M ;

Körner, M ;

Mishal, Z ;

Ganné, F ;

Vannier, JP ;

Soria, J ;

Soria, C .

CARCINOGENESIS, 2001, 22 (08) :1139-1148

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