Human Gene Set: FREDERICK_PRKCI_TARGETS

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Standard name FREDERICK_PRKCI_TARGETS
Systematic name M13167
Brief description Genes down-regulated in H1703 cells (non-small cell lung cancer, NSCLC) after knockdown of PRKCI [GeneID=5584] by RNAi.
Full description or 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-Par6alpha-Rac1 signaling axis that drives anchorage-independent growth and invasion of NSCLC cells through induction of MMP-10 expression.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18427549   Authors: Frederick LA,Matthews JA,Jamieson L,Justilien V,Thompson EA,Radisky DC,Fields AP
Exact source Table 1
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Organism Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
Source platform Human_RefSeq
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Version history 3.0: First introduced

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