KIBRA (WWC1) Is a Metastasis Suppressor Gene Affected by Chromosome 5q Loss in Triple-Negative Breast Cancer.

Autor:	Knight JF; Goodman Cancer Research Centre, McGill University, Montreal, QC H3G 0B1, Canada., Sung VYC; Goodman Cancer Research Centre, McGill University, Montreal, QC H3G 0B1, Canada; Department of Biochemistry, McGill University, Montreal, QC H2W 1S6, Canada., Kuzmin E; Goodman Cancer Research Centre, McGill University, Montreal, QC H3G 0B1, Canada; Department of Biochemistry, McGill University, Montreal, QC H2W 1S6, Canada., Couzens AL; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada., de Verteuil DA; Goodman Cancer Research Centre, McGill University, Montreal, QC H3G 0B1, Canada., Ratcliffe CDH; Goodman Cancer Research Centre, McGill University, Montreal, QC H3G 0B1, Canada; Department of Biochemistry, McGill University, Montreal, QC H2W 1S6, Canada., Coelho PP; Goodman Cancer Research Centre, McGill University, Montreal, QC H3G 0B1, Canada; Department of Biochemistry, McGill University, Montreal, QC H2W 1S6, Canada., Johnson RM; Goodman Cancer Research Centre, McGill University, Montreal, QC H3G 0B1, Canada., Samavarchi-Tehrani P; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada., Gruosso T; Goodman Cancer Research Centre, McGill University, Montreal, QC H3G 0B1, Canada; Department of Oncology, McGill University, Montreal, QC H2W 1S6, Canada., Smith HW; Goodman Cancer Research Centre, McGill University, Montreal, QC H3G 0B1, Canada., Lee W; Department of Biomedical Engineering, McGill University, Montreal, QC H3A 2B4, Canada., Saleh SM; Goodman Cancer Research Centre, McGill University, Montreal, QC H3G 0B1, Canada., Zuo D; Goodman Cancer Research Centre, McGill University, Montreal, QC H3G 0B1, Canada., Zhao H; Goodman Cancer Research Centre, McGill University, Montreal, QC H3G 0B1, Canada., Guiot MC; Montreal Neurological Institute, Department of Pathology, McGill University, Montreal, QC H3A 2B4, Canada., Davis RR; Department of Pathology and Laboratory Medicine, University of California at Davis School of Medicine, Sacramento, CA 95817, USA., Gregg JP; Department of Pathology and Laboratory Medicine, University of California at Davis School of Medicine, Sacramento, CA 95817, USA., Moraes C; Goodman Cancer Research Centre, McGill University, Montreal, QC H3G 0B1, Canada; Department of Biomedical Engineering, McGill University, Montreal, QC H3A 2B4, Canada; Department of Chemical Engineering, McGill University, Montreal, QC H3A 0C5, Canada., Gingras AC; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada., Park M; Goodman Cancer Research Centre, McGill University, Montreal, QC H3G 0B1, Canada; Department of Biochemistry, McGill University, Montreal, QC H2W 1S6, Canada; Department of Oncology, McGill University, Montreal, QC H2W 1S6, Canada. Electronic address: morag.park@mcgill.ca.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2018 Mar 20; Vol. 22 (12), pp. 3191-3205.
DOI:	10.1016/j.celrep.2018.02.095
Abstrakt:	Triple-negative breast cancers (TNBCs) display a complex spectrum of mutations and chromosomal aberrations. Chromosome 5q (5q) loss is detected in up to 70% of TNBCs, but little is known regarding the genetic drivers associated with this event. Here, we show somatic deletion of a region syntenic with human 5q33.2-35.3 in a mouse model of TNBC. Mechanistically, we identify KIBRA as a major factor contributing to the effects of 5q loss on tumor growth and metastatic progression. Re-expression of KIBRA impairs metastasis in vivo and inhibits tumorsphere formation by TNBC cells in vitro. KIBRA functions co-operatively with the protein tyrosine phosphatase PTPN14 to trigger mechanotransduction-regulated signals that inhibit the nuclear localization of oncogenic transcriptional co-activators YAP/TAZ. Our results argue that the selective advantage produced by 5q loss involves reduced dosage of KIBRA, promoting oncogenic functioning of YAP/TAZ in TNBC. (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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