Caspases in apoptosis and beyond

Li, J; Yuan, Junying

doi:10.1038/onc.2008.297

Cited by 898 publications

(763 citation statements)

References 119 publications

Supporting

Mentioning

737

Contrasting

Unclassified

Order By: Relevance

“…In addition, WIF1 expression induced significant apoptosis ( Figure 3c). Caspases have a major role in regulating apoptotic cell death (Li and Yuan, 2008), and we observed a significant increase in caspase-3/7 activity after WIF1 transfection (Figure 3d). …”

Section: Wif1 Downregulation Is Frequent and Occurs Early In Human Cementioning

confidence: 63%

Wnt inhibitory factor 1 induces apoptosis and inhibits cervical cancer growth, invasion and angiogenesis in vivo

et al. 2011

View full text Add to dashboard Cite

Aberrant activation of Wingless-type (Wnt)/b-catenin signaling is widespread in human cervical cancer. However, the underlying mechanisms of Wnt activation and the therapeutic potential of Wnt inhibition remain largely unknown. Here, we demonstrate that the Wnt inhibitory factor 1 (WIF1), a secreted Wnt antagonist, is downregulated in all human primary cervical tumors and cell lines analyzed. Our data reveal that WIF1 downregulation occurs due to promoter hypermethylation and is an early event in cervical oncogenesis. WIF1 re-expression upon 5-aza-2 0 -deoxycytidine treatment or WIF1 gene transfer induces significant apoptosis and G 2 /M arrest, and inhibits cervical cancer cell proliferation in vitro. Consistent with this, treatment of established mice tumor xenografts with peritumoral WIF1 gene transfer results in a significant inhibition of cancer growth and invasion. WIF1 treatment causes a significant decrease in intracellular WNT1 and TCF-4 proteins revealing novel Wnt-regulatory mechanisms. Thus, WIF1 causes a major cellular re-distribution of b-catenin and a significant inhibition of the Wnt/b-catenin pathway in tumor cells, as documented by a remarkable reversion in the expression of Wnt/b-catenin transcriptional target genes (E-cadherin, c-Myc, cyclin D1, CD44 and VEGF). Consequently, multiple critical events in tumor progression and metastasis such as cell proliferation, angiogenesis and invasion were inhibited by WIF1. In addition, WIF1 modulated the expression of specific anti-apoptotic and apoptotic proteins, thereby inducing significant apoptosis in vivo. Our findings demonstrate for the first time that WIF1 downregulation by epigenetic gene silencing is an important mechanism of Wnt activation in cervical oncogenesis. Of major clinical relevance, we show that peritumoral WIF1 gene transfer reduces not only cancer growth but also invasion in well-established tumors. Therefore, our data provide novel mechanistic insights into the role of WIF1 in cervical cancer progression, and the important preclinical validation of WIF1 as a potent drug target in cervical cancer treatment.

show abstract

Section: Wif1 Downregulation Is Frequent and Occurs Early In Human Cementioning

confidence: 63%

Wnt inhibitory factor 1 induces apoptosis and inhibits cervical cancer growth, invasion and angiogenesis in vivo

et al. 2011

View full text Add to dashboard Cite

show abstract

“…The extrinsic pathway receives signals through the binding of extracellular protein ligands to proapoptotic death receptors (DRs), located on the cell surface (Ashkenazi and Dixit, 1998). Both pathways lead to hierarchical activation of specialized cysteine-aspartate proteases called caspases (Lavrik et al, 2005b;Li and Yuan, 2008). Apoptotic signals first activate initiator caspases, including caspase-2, -8, -9 and -10, by inducing their oligomerization at multiprotein platforms (Chen et al, 2002;Boatright et al, 2003;Bouchier-Hayes et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

New insights into apoptosis signaling by Apo2L/TRAIL

2010

View full text Add to dashboard Cite

“…These enzymes are present in pro-forms under non-apoptotic conditions and are activated by cleavage to have protease activities (Li and Yuan, 2008). Both the mitochondrial intrinsic pathway and the death receptormediated extrinsic pathway converge to activate caspases.…”

Section: Introductionmentioning

confidence: 99%

Differential apoptotic activities of wild-type FOXL2 and the adult-type granulosa cell tumor-associated mutant FOXL2 (C134W)

et al. 2010

View full text Add to dashboard Cite

Some mutations in FOXL2 result in premature ovarian failure accompanied by blepharophimosis, ptosis, epicanthus inversus syndrome type I disease, and FOXL2-null mice exhibit developmental defects in granulosa cells. Recently, FOXL2 c.402C4G, a new somatic mutation that leads to a p.C134W change, was found in the majority of adult-type ovarian granulosa cell tumors (GCTs). In this study, we investigated the possible mechanisms by which the C134W mutation contributes to the development of GCTs. Wild-type (WT) and mutant FOXL2 displayed differential apoptotic activities. Specifically, WT FOXL2 induced significant granulosa cell death, but the mutant exhibited minimal cell death. The FOXL2-induced apoptotic response was greatly dependent on caspase 8, BID and BAK because the depletion of any of these three proteins inhibited FOXL2 from eliciting the full apoptotic response. Activation of caspase 8 and subsequent increased production of truncated BID, and oligomerization of BAK, and release of cytochrome c were all associated with the apoptosis induced by WT FOXL2 expression. In contrast, the mutant FOXL2 was unable to elicit the full array of apoptotic signaling responses. In addition, we found differential TNF-R1 (tumor necrosis factor-receptor 1) and Fas (CD95/APO-1) upregulation between the WT and the mutant, and the silencing of TNF-R1 or Fas and the blockage of the death signaling mediated by TNF-R1 or Fas using TNF-Fc or Fas-Fc, respectively, resulted in significant attenuations of FOXL2-induced apoptosis. Moreover, granulosa cells that expressed either WT FOXL2 or mutant exhibited distinct cell death sensitivities on activation of death receptors and deprivation of serum. Thus, the differential activities of FOXL2 and its mutant may partially account for the pathophysiology of GCT development.

show abstract

Caspases in apoptosis and beyond

Cited by 898 publications

References 119 publications

Wnt inhibitory factor 1 induces apoptosis and inhibits cervical cancer growth, invasion and angiogenesis in vivo

Wnt inhibitory factor 1 induces apoptosis and inhibits cervical cancer growth, invasion and angiogenesis in vivo

New insights into apoptosis signaling by Apo2L/TRAIL

Differential apoptotic activities of wild-type FOXL2 and the adult-type granulosa cell tumor-associated mutant FOXL2 (C134W)

Contact Info

Product

Resources

About