Matrix metalloproteinase-10 is a critical effector of protein kinase Ciota-Par6alpha-mediated lung cancer.

Oncogene
L A FrederickAlan P Fields

Abstract

Protein kinase Ciota (PKCiota) drives transformed growth of non-small cell lung cancer (NSCLC) cells through the Rho family GTPase Rac1. We show here that PKCiota activates Rac1 in NSCLC cells by formation of a PKCiota-Par6alpha complex that drives anchorage-independent growth and invasion through activation of matrix metalloproteinase-10 (MMP-10) expression. RNAi-mediated knockdown of PKCiota, Par6alpha or Rac1 expression inhibits NSCLC transformation and MMP-10 expression in vitro. Expression of wild-type Par6alpha in Par6alpha-deficient cells restores transformation and MMP-10 expression, whereas expression of Par6alpha mutants that either cannot bind PKCiota (Par6alpha-K19A) or couple to Rac1 (Par6alpha-DeltaCRIB) do not. Knockdown of MMP-10 expression blocks anchorage-independent growth and invasion of NSCLC cells and addition of catalytically active MMP-10 to PKCiota- or Par6alpha-deficient cells restores anchorage-independent growth and invasion. Dominant-negative PKCiota inhibits tumorigenicity and MMP-10 expression in subcutaneous NSCLC tumors. MMP-10 and PKCiota are coordinately overexpressed in primary NSCLC tumors, and tumor MMP-10 expression predicts poor survival in NSCLC patients. Our data define a PKCiota-Par6al...Continue Reading

References

Jun 19, 1991·International Journal of Cancer. Journal International Du Cancer·D MullerJ Abecassis
Aug 10, 2000·Nature Cell Biology·G JobertyI G Macara
Aug 21, 2001·Biochemical and Biophysical Research Communications·I ImotoJ Inazawa
Nov 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·M E GarberI Petersen
May 7, 2002·Nature Reviews. Cancer·Mikala Egeblad, Zena Werb
Sep 25, 2002·Cancer Detection and Prevention·Robin MathewRanju Ralhan
Dec 3, 2003·Oncogene·Nam Hoon ChoSang Ho Cho
Sep 10, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Céline Van ThemscheYves St-Pierre
Feb 22, 2005·Neoplasia : an International Journal for Oncology Research·Jason H GillPaul M Loadman
Jun 25, 2005·Seminars in Cancer Biology·Hynda K Kleinman, George R Martin
Jul 5, 2005·The Journal of Biological Chemistry·Roderick P RegalaAlan P Fields
Oct 6, 2005·Cancer Research·Roderick P RegalaAlan P Fields
Jul 25, 2006·The Journal of Biological Chemistry·Eda ErdoganAlan P Fields
Jun 16, 2007·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Alan P Fields, Roderick P Regala

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Citations

Jul 12, 2011·Inflammatory Bowel Diseases·Shelly R CalcagnoNicole R Murray
Feb 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·Federica ChianaleAndrea Graziani
Dec 30, 2010·The Journal of Biological Chemistry·Verline JustilienAlan P Fields
Feb 19, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Eda ErdoganAlan P Fields
Oct 15, 2011·PloS One·Elsayed Mohamed DerazTakashi Takata
Feb 24, 2012·PloS One·Michele L ScottiNicole R Murray
Nov 19, 2009·Journal of Biomedicine & Biotechnology·Kieran BrennanAnn M Hopkins
Dec 18, 2013·Oncogene·R GargM G Kazanietz
Oct 26, 2012·Cellular and Molecular Life Sciences : CMLS·Helan Xiao, Mingyao Liu
Jan 13, 2016·Advances in Biological Regulation·Alan P FieldsNicole R Murray
Nov 22, 2011·Molecular Aspects of Medicine·Diego SbardellaMassimo Coletta
Mar 27, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Oihane García-IrigoyenMatias A Avila
Oct 15, 2010·Journal of Cellular Physiology·Nicole R MurrayAlan P Fields
Jul 25, 2013·Cell Adhesion & Migration·Adrian Gunaratne, Gianni M Di Guglielmo
Nov 10, 2009·Advances in Enzyme Regulation·Alan P Fields, Verline Justilien
Nov 16, 2013·Biochemical Pharmacology·Peter J ParkerAlan P Fields
Jun 2, 2016·Small GTPases·Alan P FieldsNicole R Murray
Jul 1, 2016·Journal of Cellular Biochemistry·Carlis RejonLuke McCaffrey
Jan 24, 2017·Cancer Cell·Verline JustilienAlan P Fields
Jan 15, 2017·Proteomics. Clinical Applications·Dandan LinghuXiaoxin Li
May 21, 2015·Cancer Informatics·Wan-Hsin LinPanos Z Anastasiadis
Sep 10, 2009·Nanotechnology·L M JongD N Jamieson
Mar 19, 2014·Oncogene·R Halaoui, L McCaffrey
Feb 13, 2016·Oncotarget·Aneta GandalovičováJan Brábek

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