Emerging roles of ADAM and ADAMTS metalloproteinases in cancer

Rocks, Natacha; Paulissen, Geneviève; Hour, Mehdi El; Quesada, F.; Crahay, Céline; Guéders, Maud; Foidart, Jean Michel; Noël, Agnès; Cataldo, Didier

doi:10.1016/j.biochi.2007.08.008

Cited by 229 publications

(188 citation statements)

References 158 publications

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“…The finding that MMP-14 and -19 are unique to 21D1-Exos and not observed in our previously published MDCK/21D1 secretome analysis (24), may represent a mechanism that allows exosome-bound proteases to traffic and function at distant/metastatic sites. ADAM proteases contain MMP-like catalytic domains (83) and are important mediators of cell surface protein shedding during tumor progression (84). Interestingly, ADAM10 has been shown to be an active vesicle-based protease, cleaving cell adhesion molecule L1 at the cell surface, and subsequently promoting cell migration (85).…”

Section: Exosomes Contain Metastatic Niche Factors Following Oncogenimentioning

confidence: 99%

Oncogenic H-Ras Reprograms Madin-Darby Canine Kidney (MDCK) Cell-derived Exosomal Proteins Following Epithelial-Mesenchymal Transition

Tauro

Mathias

Greening

et al. 2013

Molecular & Cellular Proteomics

168

171

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Epithelial-mesenchymal transition (EMT) is a highly con- Epithelial-mesenchymal transition (EMT)1 is a cellular process whereby otherwise sessile epithelial cells undergo a shift in plasticity and acquire the ability to disseminate (1-6). Hallmarks of EMT include diminished expression of cell-cell contact and adhesion components (e.g. E-cadherin), diminished expression of cell-matrix components, decreased expression of components involved in cell polarity, elevated expression of proteins involved in cytoskeleton remodelling (e.g. vimentin), and increased expression of various matrix metalloproteinFrom the ‡Department of Biochemistry,

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Section: Exosomes Contain Metastatic Niche Factors Following Oncogenimentioning

confidence: 99%

Oncogenic H-Ras Reprograms Madin-Darby Canine Kidney (MDCK) Cell-derived Exosomal Proteins Following Epithelial-Mesenchymal Transition

Tauro

Mathias

Greening

et al. 2013

Molecular & Cellular Proteomics

168

171

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“…A disintegrins and metalloproteinases with thrombospondin motifs (ADAMTS), a family of extracellular metalloproteases, is structurally and functionally similar to matrix metalloproteinases (MMP) and ADAMs (7). Unlike ADAMs mainly as trans-membrane proteins, ADAMTSs are secreted proteinases binding to ECM (8). Dysregulated expression of ADAMTSs, such as ADAMTS1 (2), ADAMTS8, ADAMTS9 (5), ADAMTS12 (3), ADAMTS15 (4), ADAMTS18 (6), and ADAMTS20 (9,10), have been detected in diverse types of malignancies including lung, brain, breast, gastric, prostate, pancreatic cancers, and glioblastoma (8).…”

Section: Introductionmentioning

confidence: 99%

“…Unlike ADAMs mainly as trans-membrane proteins, ADAMTSs are secreted proteinases binding to ECM (8). Dysregulated expression of ADAMTSs, such as ADAMTS1 (2), ADAMTS8, ADAMTS9 (5), ADAMTS12 (3), ADAMTS15 (4), ADAMTS18 (6), and ADAMTS20 (9,10), have been detected in diverse types of malignancies including lung, brain, breast, gastric, prostate, pancreatic cancers, and glioblastoma (8). Various ADAMTSs have been shown to regulate cell proliferation, adhesion, migration, angiogenesis, and intracellular signaling (8,11), thus involved in multiple tumor pathogenesis (1,6).…”

Section: Introductionmentioning

confidence: 99%

The Metalloprotease ADAMTS8 Displays Antitumor Properties through Antagonizing EGFR–MEK–ERK Signaling and Is Silenced in Carcinomas by CpG Methylation

Choi

Wang

et al. 2014

Molecular Cancer Research

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A disintegrins and metalloproteinases with thrombospondin motifs (ADAMTS) family members have been reported dysregulated in various cancers. Through refining a loss of heterozygosity locus at 11q25 by array-CGH, we identified ADAMTS8 as a novel candidate tumor suppressor gene. Although ADAMTS8 downregulation has been reported in several tumors, its biologic function and underlying mechanism remain largely unknown. Here, we found that ADAMTS8 is broadly expressed in normal tissues but frequently downregulated or silenced by promoter methylation in common carcinoma cell lines, including nasopharyngeal, esophageal squamous cell, gastric, and colorectal carcinomas. Pharmacologic or genetic demethylation restored ADAMTS8 expression, indicating that promoter methylation mediates its silencing. Aberrant methylation of ADAMTS8 was also detected in several types of primary tumors but rarely in normal tissues. Further functional studies showed that restoring ADAMTS8 expression suppressed tumor cell clonogenicity through inducing apoptosis. ADAMTS8 as a secreted protease inhibited epidermal growth factor receptor (EGFR) signaling along with decreased levels of phosphorylated MEK and ERK. We further found that ADAMTS8 disrupted actin stress fiber organization and inhibited tumor cell motility. Thus, our data demonstrate that ADAMTS8 metalloprotease acts as a functional tumor suppressor through antagonizing EGFR-MEK-ERK signaling, in addition to its previously reported anti-angiogenesis function, and is frequently methylated in common tumors.

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“…However, the contribution of desmosomal cadherin regulation to epithelial remodeling via endocytic trafficking has not been addressed, nor is the involvement of RTKs or MMPs understood. The importance of RTKs and MMPs in epithelial remodeling processes is highlighted by the well-established role of erbB family members in tumor progression and recent recognition that ADAM family members are aberrantly expressed in certain cancers (Borrell-Pages et al, 2003;Rocks et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

EGFR and ADAMs Cooperate to Regulate Shedding and Endocytic Trafficking of the Desmosomal Cadherin Desmoglein 2

Klessner

Desai

Amargo³

et al. 2009

MBoC

104

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Regulation of classic cadherins plays a critical role in tissue remodeling during development and cancer; however, less attention has been paid to the importance of desmosomal cadherins. We previously showed that EGFR inhibition results in accumulation of the desmosomal cadherin, desmoglein 2 (Dsg2), at cell-cell interfaces accompanied by inhibition of matrix metalloprotease (MMP)-dependent shedding of the Dsg2 ectodomain and tyrosine phosphorylation of its cytoplasmic domain. Here, we show that EGFR inhibition stabilizes Dsg2 at intercellular junctions by interfering with its accumulation in an internalized cytoplasmic pool. Furthermore, MMP inhibition and ADAM17 RNAi, blocked shedding and depleted internalized Dsg2, but less so E-cadherin, in highly invasive SCC68 cells. ADAM9 and 15 silencing also impaired Dsg2 processing, supporting the idea that this desmosomal cadherin can be regulated by multiple ADAM family members. In contrast, ADAM10 siRNA enhanced accumulation of a 100-kDa Dsg2 cleavage product and internalized pool of Dsg2. Although both MMP and EGFR inhibition increased intercellular adhesive strength in control cells, the response to MMP-inhibition was Dsg2-dependent. These data support a role for endocytic trafficking in regulating desmosomal cadherin turnover and function and raise the possibility that internalization and regulation of desmosomal and classic cadherin function can be uncoupled mechanistically. INTRODUCTIONThe ability of cells to modulate their contacts with each other and the underlying matrix is essential for epithelial remodeling that occurs in development and cancer progression (Behrens, 1999;Thiery, 2003;Kramer et al., 2005). In particular, members of cadherin family of calcium-dependent intercellular adhesion molecules have been demonstrated to both suppress (Frixen et al., 1991) and promote (Islam et al., 1996) cell migration and invasion. Although classic cadherins assemble into intercellular adhesive structures known as adherens junctions that associate with the cortical actin cytoskeleton, desmosomal cadherins, including desmogleins and desmocollins, make up the adhesive core of desmosomes, which anchor intermediate filaments (IF) to sites of strong intercellular adhesion (Green and Simpson, 2007).Anchorage to the IF cytoskeleton is established with the cooperation of the desmosomal cadherin-associated proteins plakoglobin and plakophilins, which in turn link the IF-associated protein desmoplakin (DP) to the membrane complex. Desmosomes provide mechanical integrity to epithelial and heart tissues by redistributing the forces of mechanical stress . In addition, desmosomal cadherins have more recently emerged as playing a role in tissue morphogenesis (Runswick et al., 2001;Chidgey and Dawson, 2007;Dusek et al., 2007).In spite of desmosomes' importance in tissue function, most studies have focused on the contribution of classic cadherins to epithelial remodeling. Classic cadherins engage in bidirectional signaling with receptor tyrosine kinases (RTKs), whereby they are both ...

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Emerging roles of ADAM and ADAMTS metalloproteinases in cancer

Cited by 229 publications

References 158 publications

Oncogenic H-Ras Reprograms Madin-Darby Canine Kidney (MDCK) Cell-derived Exosomal Proteins Following Epithelial-Mesenchymal Transition

Oncogenic H-Ras Reprograms Madin-Darby Canine Kidney (MDCK) Cell-derived Exosomal Proteins Following Epithelial-Mesenchymal Transition

The Metalloprotease ADAMTS8 Displays Antitumor Properties through Antagonizing EGFR–MEK–ERK Signaling and Is Silenced in Carcinomas by CpG Methylation

EGFR and ADAMs Cooperate to Regulate Shedding and Endocytic Trafficking of the Desmosomal Cadherin Desmoglein 2

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