Plakophilin3 downregulation leads to a decrease in cell adhesion and promotes metastasis

International Journal of Cancer. Journal International Du Cancer
Samrat T KunduSorab N Dalal

Abstract

Plakophilin3 is a desmosomal plaque protein whose levels are reduced in poorly differentiated tumors of the oropharyngeal cavity and in invasive colon carcinomas. To test the hypothesis that plakophilin3 loss stimulates neoplastic progression, plakophilin3 expression was inhibited by DNA vector driven RNA interference in 3 epithelial cell lines, HCT116, HaCaT and fetal buccal mucosa. The plakophilin3-knockdown clones showed a decrease in cell-cell adhesion as assessed in a hanging drop assay, which was accompanied by an increase in cell migration. The HCT116 plakophilin3-knockdown clones showed a decrease in desmosome size as revealed by electron microscopy. These altered desmosomal properties were accompanied by colony formation in soft agar and growth to high density in culture. The HCT116-derived clones showed accelerated tumor formation in nude mice and increased metastasis to the lung, a phenotype consistent with the increased migration observed in vitro and is consistent with data from human tumors that suggests that plakophililn3 is lost in invasive and metastatic tumors. These data indicate that plakophilin3 loss leads to a decrease in cell-cell adhesion leading to the stimulation of neoplastic progression and metastasis.

References

Oct 1, 1995·Molecular and Cellular Biology·J Zalvide, J A DeCaprio
May 18, 1999·Molecular and Cellular Biology·S N DalalJ A DeCaprio
Aug 10, 1999·Nature·L ChinR A DePinho
Oct 6, 1999·Current Opinion in Cell Biology·S M Troyanovsky
Mar 17, 2001·Nature Reviews. Molecular Cell Biology·K J Green, C A Gaudry
Jun 21, 2001·Proceedings of the National Academy of Sciences of the United States of America·C MertensW W Franke
Sep 17, 2002·Current Opinion in Cell Biology·David R GarrodZhuxiang Nie
Apr 23, 2003·The Journal of Cell Biology·Stefan BonnéFrans van Roy
May 3, 2003·Carcinogenesis·Mirian BrinkPiet A van den Brandt
Feb 1, 1961·The Journal of Biophysical and Biochemical Cytology·J H LUFT
Jul 15, 2004·International Journal of Cancer. Journal International Du Cancer·Ujwala RaulMilind Vaidya
Mar 31, 2005·Cell·Rebecca A IhrieLaura D Attardi
Apr 12, 2005·European Journal of Cell Biology·Ansgar Schmidt, Stephanie Jäger
Jun 21, 2005·Molecular and Cellular Biology·Jeffrey R SkaarJames A DeCaprio
Aug 3, 2005·Cancer Research·Michelle R MarquesLaura D Attardi
Aug 17, 2005·Cancer Research·Chiyuki FurukawaYusuke Nakamura
Jun 13, 2006·Biochimica Et Biophysica Acta·Mechthild Hatzfeld
Nov 7, 2006·Proceedings of the National Academy of Sciences of the United States of America·Long-Cheng LiRajvir Dahiya
May 24, 2007·British Journal of Cancer·M Chidgey, C Dawson
Sep 19, 2007·Cancer Research·Vincent A PotironHarry A Drabkin
Dec 15, 2007·The Journal of Investigative Dermatology·Tatyana SklyarovaJolanda van Hengel

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Citations

Sep 29, 2011·Medical Oncology·Guzin Gonullu DemiragIdris Yucel
Apr 22, 2011·Nature Reviews. Cancer·Rachel L Dusek, Laura D Attardi
Sep 9, 2011·Molecular Biology of the Cell·Hunain AlamMilind M Vaidya
Apr 7, 2012·International Journal of Cell Biology·Zackie Aktary, Manijeh Pasdar
Feb 26, 2014·The Journal of Cell Biology·Shenhav CohenAlfred L Goldberg
Jul 16, 2010·Dermatology Research and Practice·Veronica G BeaudryLaura D Attardi
Jan 5, 2011·Frontiers in Bioscience (Landmark Edition)·Alan WellsDouglas A Lauffenburger
Sep 23, 2010·Cellular and Molecular Life Sciences : CMLS·Prajakta GosaviSorab N Dalal
Jan 28, 2014·Cell Communication & Adhesion·Mechthild HatzfeldRené Keil
Nov 12, 2013·Cell Communication & Adhesion·Robert M Harmon, Kathleen J Green
Dec 10, 2015·The International Journal of Biochemistry & Cell Biology·Crismita DmelloMilind Vaidya
Jun 18, 2011·Molecular Carcinogenesis·Jiangli ChenPeter J Koch
Jul 28, 2013·Current Opinion in Cell Biology·Byung-Min ChungPierre A Coulombe
May 11, 2015·Breast Cancer Research and Treatment·Lingeng LuWenxue Ma
Jun 3, 2016·Scientific Reports·Amitabha MukhopadhyaySorab N Dalal
Aug 14, 2009·Current Opinion in Cell Biology·Amanda E Bass-ZubekKathleen J Green
Sep 17, 2014·Molecular and Cellular Biology·Regina Fischer-KešoIlse Hofmann
Feb 16, 2012·British Journal of Cancer·M P MyklebustO Dahl
Jun 5, 2016·The Journal of Biological Chemistry·Kumarkrishna RaychaudhuriSorab N Dalal
Feb 8, 2018·Annual Review of Pathology·Nicole A Najor
Dec 12, 2019·Oncogene·Joel Martin-PadronPedro P Medina
Dec 19, 2019·Cell and Tissue Research·Ilse Hofmann
Oct 17, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lennard Y W LeeIan Tomlinson
Jan 8, 2021·BMC Gastroenterology·Tingting YangZhenqing Feng
Apr 5, 2021·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Arunabha BoseSorab N Dalal
Jun 20, 2021·International Journal of Cancer. Journal International Du Cancer·Nazia ChaudharySorab N Dalal

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