title: Fluid shear stress activates YAP1 to promote cancer cell motility.
abstract: Mechanical stress is pervasive in egress routes of malignancy, yet the intrinsic effects of force on tumour cells remain poorly understood. Here, we demonstrate that frictional force characteristic of flow in the lymphatics stimulates YAP1 to drive cancer cell migration; whereas intensities of fluid wall shear stress (WSS) typical of venous or arterial flow inhibit taxis. YAP1, but not TAZ, is strictly required for WSS-enhanced cell movement, as blockade of YAP1, TEAD1-4 or the YAP1-TEAD interaction reduces cellular velocity to levels observed without flow. Silencing of TEAD phenocopies loss of YAP1, implicating transcriptional transactivation function in mediating force-enhanced cell migration. WSS dictates expression of a network of YAP1 effectors with executive roles in invasion, chemotaxis and adhesion downstream of the ROCK-LIMK-cofilin signalling axis. Altogether, these data implicate YAP1 as a fluid mechanosensor that functions to regulate genes that promote metastasis.
authors.affiliation: Children's Regenerative Medicine Program, Department of Pediatric Surgery, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.|Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Children's Regenerative Medicine Program, Department of Pediatric Surgery, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.|Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
authors.forename: Miguel F
authors.initials: MF
authors.lastname: Diaz
authors.affiliation: Department of BioSciences, Rice University, Houston, Texas 77030, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Price
authors.affiliation: Department of BioSciences, Rice University, Houston, Texas 77030, USA.
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Ozuna
authors.affiliation: Department of Pathology, The University of Texas Medical School, Houston, Texas 77030, USA.
authors.forename: Songlin
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Sevick-Muraca
authors.affiliation: Vivian L. Smith Department of Neurosurgery, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Hagan
authors.affiliation: Children's Regenerative Medicine Program, Department of Pediatric Surgery, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.|Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
authors.forename: Pamela L
authors.identifier: 0000-0002-4530-015X
authors.initials: PL
authors.lastname: Wenzel
mesh_terms: D051339:Actin Depolymerizing Factors / Q000235:genetics / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D045604:Extracellular Fluid / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D054461:Lim Kinases / Q000235:genetics / Q000378:metabolism; D042601:Lymphatic Vessels / Q000737:chemistry / Q000378:metabolism; D008297:Male; D040542:Mechanotransduction, Cellular; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013314:Stress, Mechanical; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000091102:YAP-Signaling Proteins
chemical_list: D051339:Actin Depolymerizing Factors; D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; C101205:TEAD2 protein, human; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C515892:LIMK1 protein, human; D054461:Lim Kinases