title: Resveratrol suppresses breast cancer cell invasion by inactivating a RhoA/YAP signaling axis.
abstract: 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.
authors.affiliation: Department of Pharmacology, College of Medicine, Konyang University, Daejeon, Korea.
authors.forename: Yu Na
authors.initials: YN
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, College of Medicine, Konyang University, Daejeon, Korea.
authors.forename: So Ra
authors.initials: SR
authors.lastname: Choe
authors.affiliation: Department of Pharmacology, College of Medicine, Konyang University, Daejeon, Korea.
authors.forename: Kyung Hwa
authors.initials: KH
authors.lastname: Cho
authors.affiliation: Department of Hematology and Oncology, Konyang University College of Medicine, Daejeon, Korea.
authors.forename: Do Yeun
authors.initials: DY
authors.lastname: Cho
authors.affiliation: Department of Pharmacology, College of Medicine, Konyang University, Daejeon, Korea.
authors.forename: Jaeku
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Pharmacology, College of Medicine, Konyang University, Daejeon, Korea.
authors.forename: Chang Gyo
authors.initials: CG
authors.lastname: Park
authors.affiliation: Department of Pharmacology, College of Medicine, Konyang University, Daejeon, Korea.
authors.forename: Hoi Young
authors.initials: HY
authors.lastname: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control*; D010750:Phosphoproteins / Q000378:metabolism*; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000972:Antineoplastic Agents, Phytogenic; D010750:Phosphoproteins; D013267:Stilbenes; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C066737:RHOA protein, human; D020742:rhoA GTP-Binding Protein; D000077185:Resveratrol