Matrix metalloproteinase-10 is a critical effector of protein kinase Cι-Par6α-mediated lung cancer

Frederick, Lori; Matthews, J. A.; Jamieson, Lee; Justilien, Verline; Thompson, E. Aubrey; Radisky, Derek C.; Fields, Alan P.

doi:10.1038/onc.2008.119

Cited by 87 publications

(180 citation statements)

References 22 publications

Supporting

Mentioning

169

Contrasting

Order By: Relevance

“…MMP-3 also contributes to epithelialmesenchymal conversion of mammary epithelial cells through cleavage of E-cadherin (2). Recently, Frederick and colleagues (25) reported that MMP-10 contributes to anchorage-independent growth of NSCLC through a PKCι-dependent pathway. Importantly, both MMP-3 and MMP-10 can activate latent MMP-1 (26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

CCAAT Enhancer Binding Protein-β Regulates Matrix Metalloproteinase-1 Expression in Interleukin-1β–Stimulated A549 Lung Carcinoma Cells

Armstrong¹,

Phelps²,

Vincenti³

2009

Molecular Cancer Research

View full text Add to dashboard Cite

Matrix metalloproteinase-1 (MMP-1) is an inflammationinducible neutral protease that mediates extracellular matrix remodeling and promotes tumor invasion. In this study, we examined the activation of MMP-1 gene expression in A549 lung carcinoma cells stimulated with the inflammatory cytokine interleukin-1β (IL-1β). We found that MMP-1 mRNA levels were maximal following 16 hours of IL-1β stimulation and that this correlated with the expression of the transcription factor CCAAT enhancer-binding protein-β (CEBPB). Knockdown of CEBPB expression with short hairpin RNA abrogated the expression of MMP-1, MMP-3, and MMP-10 in IL-1β-stimulated A549 cells. An established CEBP element in the MMP-1 promoter was found to be required for basal and IL-1β-induced transcription. Electrophoresis mobility shift assays showed that CEBPB binds to this promoter element maximally 16 hours after IL-1β stimulation. DNA affinity chromatography studies showed that the LAP1, LAP2, and LIP isoforms of CEBPB bind to the IL-1β-responsive CEBPB site in the MMP-1 promoter. Exogenous expression of the LAP1 and LAP2 isoforms stimulated the MMP-1 promoter, whereas LIP had no effect. Phosphorylation of CEBPB at Thr 235 peaked at 16 hours in IL-1β-stimulated cells. The MEK inhibitor U0126 inhibited this phosphorylation and reduced MMP-1 gene induction. These studies establish CEBPB as an important mediator of metalloproteinase gene activation during inflammatory responses in lung cancer cells and highlight the different regulatory roles of CEBPB isoforms. (Mol Cancer Res 2009;7(9):1517-24)

show abstract

Section: Discussionmentioning

confidence: 99%

CCAAT Enhancer Binding Protein-β Regulates Matrix Metalloproteinase-1 Expression in Interleukin-1β–Stimulated A549 Lung Carcinoma Cells

Armstrong¹,

Phelps²,

Vincenti³

2009

Molecular Cancer Research

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

“…MMP-10 in particular is up-regulated in human non-small cell lung carcinoma (NSCLC), where it is associated with poor clinical outcome (22,77). We have identified MMP-10 as a major downstream effector of two NSCLC oncogenes, Kras and PKC (22,23). Silencing of MMP-10 expression in lung cancer cells blocks anchorage-independent growth and invasion; interestingly, recombinant MMP-10cd reconstitutes anchorage-independent growth and invasion, whereas MMP-3cd does not, indicating that MMP-10 must have a highly specific function in mediating cellular transformation (22).…”

Section: Discussionmentioning

confidence: 99%

“…We have identified MMP-10 as a major downstream effector of two NSCLC oncogenes, Kras and PKC (22,23). Silencing of MMP-10 expression in lung cancer cells blocks anchorage-independent growth and invasion; interestingly, recombinant MMP-10cd reconstitutes anchorage-independent growth and invasion, whereas MMP-3cd does not, indicating that MMP-10 must have a highly specific function in mediating cellular transformation (22). Silencing of MMP-10 expression also suppresses the enhanced self-renewal and tumorigenic properties of the subpopulation of lung cancer cells with stemlike characteristics (87), and we further find that genetic loss of Mmp10 suppresses tumorigenesis and tumor growth in mouse models of oncogenic Kras-mediated lung adenocarcinoma (23).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Matrix Metalloproteinase-10 (MMP-10) Interaction with Tissue Inhibitors of Metalloproteinases TIMP-1 and TIMP-2

Batra

Robinson

Soares

et al. 2012

Journal of Biological Chemistry

100

105

View full text Add to dashboard Cite

Background: Stromelysins MMP-3 and MMP-10 serve distinct functions, and differential inhibition by TIMPs offers one mechanism of control.Results: MMP-10 shows reduced sensitivity to TIMP-1 and -2; the MMP-10⅐TIMP-1 structure provides insights into inhibitor specificity. Conclusion: MMP sequence homology poorly predicts TIMP affinity, where subtle conformational differences shape selectivity. Significance: Our results clarify biological protease regulation and suggest strategies for engineering TIMP selectivity.

show abstract

“…Moreover, PKCι regulates invasive behavior by activating Rac in lung cancer cells (25). Interestingly, PA, the lipid product of DGKα activity, has been reported to bind directly to PKCζ and to stimulate its enzymatic activity (20), whereas it was recently shown that DGKα enhances PKCζ-mediated phosphorylation of p65/Rel (26).…”

Section: Discussionmentioning

confidence: 99%

Diacylglycerol kinase α mediates HGF-induced Rac activation and membrane ruffling by regulating atypical PKC and RhoGDI

Chianale

Rainero

Cianflone

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Diacylglycerol kinases (DGKs) convert diacylglycerol (DAG) into phosphatidic acid (PA), acting as molecular switches between DAG-and PA-mediated signaling. We previously showed that Srcdependent activation and plasma membrane recruitment of DGKα are required for growth-factor-induced cell migration and ruffling, through the control of Rac small-GTPase activation and plasma membrane localization. Herein we unveil a signaling pathway through which DGKα coordinates the localization of Rac. We show that upon hepatocyte growth-factor stimulation, DGKα, by producing PA, provides a key signal to recruit atypical PKCζ/ι (aPKCζ/ι) in complex with RhoGDI and Rac at ruffling sites of colony-growing epithelial cells. Then, DGKα-dependent activation of aPKCζ/ι mediates the release of Rac from the inhibitory complex with RhoGDI, allowing its activation and leading to formation of membrane ruffles, which constitute essential requirements for cell migration. These findings highlight DGKα as the central element of a lipid signaling pathway linking tyrosine kinase growth-factor receptors to regulation of aPKCs and RhoGDI, and providing a positional signal regulating Rac association to the plasma membrane.cell migration | growth factors | phosphatidic acid C ell migration, central to many biological and pathological processes such as cancer metastatic progression, is a multistep cycle involving extension of protrusions and formation of stable attachments near the leading edge, followed by translocation of the cell body forward (1). The protrusive activity occurring at the leading edge depends on the spatial and temporal coordination between cell substrate adhesion and actin reorganization. Rhofamily small GTPases coordinate the recruitment at the leading edge of downstream effectors, thereby mediating the formation of ruffles and lamellipodia. Their GTP-bound state is tightly regulated by both guanine nucleotide exchange factors (GEFs), which stimulate GTP loading, and GTPase activating proteins (GAPs), which catalyze GTP hydrolysis. Moreover, Rho-family GTPases are regulated by guanine nucleotide dissociation inhibitors (GDIs), which antagonize both GEFs and GAPs and mediate the cycling of Rho proteins between the cytosol and the membrane (2, 3).Atypical protein kinase C ζ and ι (aPKCζ/ι), unlike classical and novel PKCs, feature a C1-like domain which does not bind to either diacylglycerol or phorbol esters, and have recently been proposed as key transducers for establishment of cell polarity and migration (4).Diacylglycerol kinases (DGKs), which convert diacylglycerol (DAG) to phosphatidic acid (PA), comprise a family of 10 distinct enzymes grouped into five classes, each featuring distinct regulatory domains and a highly conserved catalytic domain preceded by two cysteine-rich C1-like domains. An increasing body of evidence indicates that DGKs, by acting as terminators of diacylglyceroltriggered signaling, contribute to regulating C1 domain-containing proteins, such as classical and novel PKCs and the Rac-GAP β-chimaerin (5). ...

show abstract

Matrix metalloproteinase-10 is a critical effector of protein kinase Cι-Par6α-mediated lung cancer

Cited by 87 publications

References 22 publications

CCAAT Enhancer Binding Protein-β Regulates Matrix Metalloproteinase-1 Expression in Interleukin-1β–Stimulated A549 Lung Carcinoma Cells

CCAAT Enhancer Binding Protein-β Regulates Matrix Metalloproteinase-1 Expression in Interleukin-1β–Stimulated A549 Lung Carcinoma Cells

Matrix Metalloproteinase-10 (MMP-10) Interaction with Tissue Inhibitors of Metalloproteinases TIMP-1 and TIMP-2

Diacylglycerol kinase α mediates HGF-induced Rac activation and membrane ruffling by regulating atypical PKC and RhoGDI

Contact Info

Product

Resources

About