Tissue Inhibitor of Metalloproteinase-3 Induces a Fas-associated Death Domain-dependent Type II Apoptotic Pathway

Bond, Mark; Murphy, Gillian; Bennett, Martin R.; Newby, Andrew C.; Baker, Andrew H.

doi:10.1074/jbc.m111507200

Cited by 131 publications

(127 citation statements)

References 54 publications

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“…Overexpression of TIMP3 induces release of cytochrome-c and activates the caspase-8 and caspase-9 pathways, both resulting in cancer cell apoptosis. 21 Bond et al 21 reported that TIMP3 induces apoptosis through a Fas-associated death domain-dependent type II apoptotic pathway. On the other hand, Kallio et al 20 showed that TIMP3 is capable of inducing apoptosis in the absence of caspase-8 activation in human small cell lung carcinoma cells, suggesting other pathways besides death receptor signaling.…”

Section: Discussionmentioning

confidence: 99%

Tissue inhibitor of metalloproteinases-3 transfer suppresses malignant behaviors of colorectal cancer cells

et al. 2012

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Colorectal carcinoma is one of the most frequent cancer diseases. For patients with this type of cancer, liver metastases are the main cause of death. Therefore, new therapeutic approaches are urgently needed to improve the outcomes. We found that both mRNA and protein levels of tissue inhibitor of metalloproteinase-3 (TIMP3) were decreased significantly in colorectal cancer tissue when compared with normal mucosa, suggesting that decrease of TIMP3 expression was correlated with malignant behavior of colorectal cancer. We evaluated the power of TIMP3, a new potent multiple functional molecule, as a biotheropeutic tool to treat cancer. Adenovirus-mediated TIMP3 transduction in CT26 colon cancer model demonstrated multiple effects to arrest cancer cell growth and induced massive apoptosis. Also, adenovirally transferred TIMP3 reduced adhesion, migration and invasion behaviors of CT26 cells in vitro. In vivo data showed that TIMP3 suppressed in vivo tumor growth and that liver metastasis was significantly reduced by TIMP3 transduction. This is the first systematic preclinical study to show that TIMP3 may be a potential molecular tool for colon cancer biological therapy.

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Section: Discussionmentioning

confidence: 99%

Tissue inhibitor of metalloproteinases-3 transfer suppresses malignant behaviors of colorectal cancer cells

et al. 2012

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“…[20][21][22][23] TIMP-3 overexpression sensitizes colon carcinoma cells to TNF-a-induced apoptosis via increased TNF receptor number …”

Section: Discussionmentioning

confidence: 99%

“…23 In vascular smooth muscle cells, TIMP-3 expression leads to apoptosis dependent on functional Fasassociated death domain and is inhibited by introduction of a dominant-negative FADD mutant. 22 Exposure of melanoma cell lines to TIMP-3 (but not TIMP-1, -2 or -4) results in stabilization of three distinct death receptors, TNFR1, Fas and TRAILR1, and sensitizes these cells to apoptosis induced by their respective ligands both in vivo and in vitro. 20 Overexpression of TIMP-3 in lung cancer cells results in apoptosis and increased p53, FasL, TNFR1 and TNFR2.…”

Section: Discussionmentioning

confidence: 99%

“…19 TIMP-3 has been shown to play a role in the regulation of receptor-mediated cell death in various cell types through inhibition of metalloproteinase activity and stabilization of cell-surface death receptors. [20][21][22][23][24][25] Within the CNS, TIMP-3 is transiently expressed in embryonic cerebral cortex during the period of naturally occurring programmed cell death 26 and is upregulated and colocalized with Fas in penumbral cortical neurons undergoing apoptosis following ischemia in the adult. 9 In culture, TIMP-3 is constitutively expressed by embryonic cortical neurons 25,27 and is necessary for Fas-mediated apoptosis induced by the chemotherapeutic drug, doxorubicin.…”

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confidence: 99%

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Tissue inhibitor of metalloproteinases-3 facilitates Fas-mediated neuronal cell death following mild ischemia

Wetzel

Harms

et al. 2007

Cell Death Differ

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Tissue inhibitor of metalloproteinase-3 (TIMP-3) is a natural inhibitor of metalloproteinases involved in matrix degradation and ectodomain shedding of many cell-surface proteins, including death receptors and/or their ligands. In the present study, we examined the role of TIMP-3 in Fas-mediated neuronal cell death following cerebral ischemia, using both gene deletion and pharmacological approaches. In culture, exposure of primary cortical neurons to 2 h of oxygen-glucose deprivation (OGD) resulted in delayed neuronal cell death that was dependent on activation of the death receptor, Fas. Cortical cultures derived from timp-3 À/À mice displayed partial resistance against OGD-induced neuronal cell death and also displayed increased shedding of Fas ligand (FasL) into the culture media, compared to wild-type control cultures. Both the increased neuroprotection and increased FasL shedding in timp-3 À/À cultures were reversed by addition of exogenous metalloproteinase inhibitors, recombinant TIMP-3 or GM6001. In vivo, timp-3 À/À mice showed marked resistance to a brief (30 min) middle cerebral artery occlusion (MCAO), but were not protected against more severe lesions induced by 90 min of MCAO. These studies demonstrate that TIMP-3 facilitates Fas-mediated neuronal cell death following OGD and plays a pro-apoptotic role in mild cerebral ischemia.

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“…However, the loss of TIMP-3 function also accelerates apoptosis in the involuting mammary gland (Fata et al, 2001). It has been suggested that TIMP-3 overexpression stabilises death receptors sensitising the cell to apoptosis (Smith et al, 1997) or activating the mitochondrial apoptotic pathway in a FADD-dependent manner (Bond et al, 2002). The mechanisms by which individual TIMPs exert pro-or antiapoptotic effects will become clearer once the relevant MMP or ADAM substrates are identified.…”

Section: Cell Deathmentioning

confidence: 99%

Matrix metalloproteinases and their tissue inhibitors direct cell fate during cancer development

2003

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Matrix metalloproteinases (MMPs) were initially recognised for their extracellular matrix (ECM)-degrading capability during tissue remodelling. Their importance was further highlighted by their role in metastasis. Clinical trials have since evaluated the potential of MMP inhibitors as anticancer therapeutics, but without success. These initial studies point to the complex, multifunctional capacity of MMPs in cancer as shown by their function, not only as strident mediators of advanced malignancies, but also as effectors of early stage tumorigenesis. Research now shows that MMPs, and their tissue inhibitors, affect tumour initiation and growth through loss of cell adhesion, evasion of apoptosis, and deregulation of cell division. The extracellular nature of the metalloproteinase axis situates it as a master regulator of cell fate.

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Tissue Inhibitor of Metalloproteinase-3 Induces a Fas-associated Death Domain-dependent Type II Apoptotic Pathway

Cited by 131 publications

References 54 publications

Tissue inhibitor of metalloproteinases-3 transfer suppresses malignant behaviors of colorectal cancer cells

Tissue inhibitor of metalloproteinases-3 transfer suppresses malignant behaviors of colorectal cancer cells

Tissue inhibitor of metalloproteinases-3 facilitates Fas-mediated neuronal cell death following mild ischemia

Matrix metalloproteinases and their tissue inhibitors direct cell fate during cancer development

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