title: P-21 activated kinase 1 knockdown inhibits β-catenin signalling and blocks colorectal cancer growth.
abstract: The p21-activated kinase 1 (PAK1) plays important roles in cell growth, motility, and transformation. The aims of this study were to delineate the signalling mechanisms downstream of PAK1, and to investigate the importance of PAK1 for colorectal cancer (CRC) growth and metastasis in vivo. PAK1 knockdown in human CRC cell lines inhibited β-catenin expression, β-catenin/TCF4 transcriptional activity, and the expression of c-Myc. In mouse models PAK1 knockdown suppressed the growth and metastasis of human CRC cells by decreasing proliferation and increasing apoptosis. Our findings demonstrate for the first time the crucial role of PAK1 in CRC progression in vivo.
authors.affiliation: Department of Surgery, University of Melbourne, Austin Health, Melbourne, Victoria 3084, Australia. hong.he@unimelb.edu.au
authors.forename: Hong
authors.initials: H
authors.lastname: He
authors.forename: Nhi
authors.initials: N
authors.lastname: Huynh
authors.forename: Kevin H
authors.initials: KH
authors.lastname: Liu
authors.forename: Cathy
authors.initials: C
authors.lastname: Malcontenti-Wilson
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
authors.forename: Christopher
authors.initials: C
authors.lastname: Christophi
authors.forename: Arthur
authors.initials: A
authors.lastname: Shulkes
authors.forename: Graham S
authors.initials: GS
authors.lastname: Baldwin
mesh_terms: D000818:Animals; D017209:Apoptosis; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000556:secondary; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*; D054462:p21-Activated Kinases / Q000172:deficiency* / Q000235:genetics
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C495270:CTNNB1 protein, human; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; D051176:beta Catenin; C515903:PAK1 protein, human; D054462:p21-Activated Kinases