title: Tead and AP1 Coordinate Transcription and Motility.
abstract: The Tead family transcription factors are the major intracellular mediators of the Hippo-Yap pathway. Despite the importance of Hippo signaling in tumorigenesis, Tead-dependent downstream oncogenic programs and target genes in cancer cells remain poorly understood. Here, we characterize Tead4-mediated transcriptional networks in a diverse range of cancer cells, including neuroblastoma, colorectal, lung, and endometrial carcinomas. By intersecting genome-wide chromatin occupancy analyses of Tead4, JunD, and Fra1/2, we find that Tead4 cooperates with AP1 transcription factors to coordinate target gene transcription. We find that Tead-AP1 interaction is JNK independent but engages the SRC1-3 co-activators to promote downstream transcription. Furthermore, we show that Tead-AP1 cooperation regulates the activity of the Dock-Rac/CDC42 module and drives the expression of a unique core set of target genes, thereby directing cell migration and invasion. Together, our data unveil a critical regulatory mechanism underlying Tead- and AP1-controlled transcriptional and functional outputs in cancer cells.
authors.affiliation: Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Xiangfan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Huapeng
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Mihir
authors.initials: M
authors.lastname: Rajurkar
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Cotton
authors.affiliation: Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Ou
authors.affiliation: Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Lihua J
authors.initials: LJ
authors.lastname: Zhu
authors.affiliation: Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Hira L
authors.initials: HL
authors.lastname: Goel
authors.affiliation: Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Arthur M
authors.initials: AM
authors.lastname: Mercurio
authors.affiliation: Divisions of Pediatric Urology and Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Joo-Seop
authors.initials: JS
authors.lastname: Park
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA; Howard Hughes Medical Institute, Worcester, MA 01605, USA.
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Davis
authors.affiliation: Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA. Electronic address: junhao.mao@umassmed.edu.
authors.forename: Junhao
authors.initials: J
authors.lastname: Mao
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D016000:Cluster Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015894:Genome, Human; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D000091262:TEA Domain Transcription Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D000091262:TEA Domain Transcription Factors; C486309:TEAD4 protein, human; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D048031:JNK Mitogen-Activated Protein Kinases
keywords: AP1; Tead; invasion; transcriptional regulation
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