TIMP-3 INDUCES CELL DEATH BY STABILIZING TNF-α RECEPTORS ON THE SURFACE OF HUMAN COLON CARCINOMA CELLS

Smith, Mark R.; Kung, Hsiang Fu; Durum, Scott K.; Colburn, Nancy H.; Sun, Yi

doi:10.1006/cyto.1997.0233

Cited by 187 publications

(150 citation statements)

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“…TIMP3 is a metalloproteinase inhibitor that functions as a pro-apoptotic factor through its ability stabilize death receptors and their ligands on the cell surface by inhibiting the metalloproteinases that inactivate them [1,30]. TIMP3 has not yet been directly implicated in AD.…”

Section: Discussionmentioning

confidence: 99%

Gene expression correlates of neurofibrillary tangles in Alzheimer's disease

Dunckley

Beach²,

Ramsey

et al. 2006

Neurobiology of Aging

159

134

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Neurofibrillary tangles (NFT) constitute one of the cardinal histopathological features of Alzheimer's disease (AD). To explore in vivo molecular processes involved in the development of NFTs, we compared gene expression profiles of NFT-bearing entorhinal cortex neurons from 19 AD patients, adjacent non-NFT-bearing entorhinal cortex neurons from the same patients, and non-NFT-bearing entorhinal cortex neurons from 14 non-demented, histopathologically normal controls (ND). Of the differentially expressed genes, 225 showed progressively increased expression (AD NFT neurons > AD non-NFT neurons > ND non-NFT neurons) or progressively decreased expression (AD NFT neurons < AD non-NFT neurons < ND non-NFT neurons), raising the possibility that they may be related to the early stages of NFT formation. Immunohistochemical studies confirmed that many of the implicated proteins are dysregulated and preferentially localized to NFTs, including apolipoprotein J, interleukin-1 receptor-associated kinase 1, tissue inhibitor of metalloproteinase 3, and casein kinase 2, beta. Functional validation studies are underway to determine which candidate genes may be causally related to NFT neuropathology, thus providing therapeutic targets for the treatment of AD.

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Section: Discussionmentioning

confidence: 99%

Gene expression correlates of neurofibrillary tangles in Alzheimer's disease

Dunckley

Beach²,

Ramsey

et al. 2006

Neurobiology of Aging

159

134

View full text Add to dashboard Cite

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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%

“…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.…”

mentioning

confidence: 99%

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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TIMP-3 INDUCES CELL DEATH BY STABILIZING TNF-α RECEPTORS ON THE SURFACE OF HUMAN COLON CARCINOMA CELLS

Cited by 187 publications

References 0 publications

Gene expression correlates of neurofibrillary tangles in Alzheimer's disease

Gene expression correlates of neurofibrillary tangles in Alzheimer's disease

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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