A dual role for Caspase8 and NF-κB interactions in regulating apoptosis and necroptosis of ovarian cancer, with correlation to patient survival

Hernandez, Lídia; Kim, M K; Noonan, Anne M.; Sagher, Ethan; Kohlhammer, Holger; Wright, George W.; Lyle, L. Tiffany; Steeg, Patricia S.; Anver, Miriam R.; Bowtell, David D.L.; Annunziata, Christina M.

doi:10.1038/cddiscovery.2015.53

Cited by 34 publications

(36 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, tumors often develop resistance to apoptosis, and therefore induction of IA is not a good therapeutic option. In this context, it has been shown that weak caspase‐8 activity is associated with worse outcome in several cancer types . Indeed, inactivation of caspase‐8 by mutations, silencing or pharmacological inhibition prevents apoptosis, which in addition may result in defective danger signaling leading to evasion of IA.…”

Section: Are Necroptotic Cancer Cells Immunogenic?mentioning

confidence: 99%

“…In this context, it has been shown that weak caspase-8 activity is associated with worse outcome in several cancer types. 40,41 Indeed, inactivation of caspase-8 by mutations, silencing or pharmacological inhibition prevents apoptosis, which in addition may result in defective danger signaling 13 leading to evasion of IA. However, in such cases another form of cell death, necroptosis, comes into play but only when caspase-8 is downregulated or inhibited.…”

Section: Are Necroptotic Cancer Cells Immunogenic?mentioning

confidence: 99%

See 1 more Smart Citation

Necroptotic cell death in anti‐cancer therapy

Krysko

Aaes

Kagan

et al. 2017

Immunological Reviews

130

101

View full text Add to dashboard Cite

Necroptosis is one the best-characterized forms of regulated necrosis. Necroptosis is mediated by the kinase activities of receptor interacting protein kinase-1 and receptor interacting protein kinase-3, which eventually lead to the activation of mixed lineage kinase domain-like. Necroptosis is characterized by rapid permeabilization of the plasma membrane, which is associated with the release of the cell content and subsequent exposure of damage-associated molecular patterns (DAMPs) and cytokines/chemokines. This release underlies the immunogenic nature of necroptotic cancer cells and their ability to induce efficient anti-tumor immunity. Triggering necroptosis has become especially important in experimental cancer treatments as an alternative to triggering apoptosis because one of the hallmarks of cancer is the blockade or evasion of apoptosis. In this review, we discuss recent advances in necroptosis research and the functional consequences of necroptotic cancer cell death, with focus on its immunogenicity and its role in the activation of anti-tumor immunity. Next, we discuss the molecular mechanisms of phosphatidylserine exposure during necroptosis and its role in the recognition of necroptotic cells. We also highlight the complex role of the necroptotic pathway in tumor promotion and suppression and in metastasis. Future studies will show whether necroptosis is truly a better strategy to overcome apoptosis resistance and provide the insights needed for development of novel treatment strategies for cancer.

show abstract

Section: Are Necroptotic Cancer Cells Immunogenic?mentioning

confidence: 99%

Section: Are Necroptotic Cancer Cells Immunogenic?mentioning

confidence: 99%

Necroptotic cell death in anti‐cancer therapy

Krysko

Aaes

Kagan

et al. 2017

Immunological Reviews

130

101

View full text Add to dashboard Cite

show abstract

“…Caspase8, a member of caspases superfamily, plays a crucial role in programed cell death when activated by upstream death receptors [5,6,16]. In consideration of vital function of caspases, caspase8 gene has only been identified in a few fish species [10,14].…”

Section: Discussionmentioning

confidence: 99%

Molecular Characterization of Caspase8 in Grass Carp (Ctenopharyngodon Idella)

Zhang¹,

Gan²,

Zhang³

et al. 2018

dtbh

View full text Add to dashboard Cite

Abstract. Caspase8 is a crucial effector member of the caspases family. It is well known that caspase8 plays a vital role in apoptosis signal transduction mediated through death receptor pathway in mammals. In the present study, grass carp caspase8 (gcCasp8) coding sequence was isolated and identified. The gcCasp8 CDS and amino acid sequence shared 45.36%-80.06% and 32.5%-71.25% with its counterparts in other teleost species and mammals, respectively. Furthermore, similar to human counterpart, the gcCasp8 CDS consisted of 8 exons and 7 introns, with one exon less than zebrafish homolog. In addition, gcCasp8 possessed caspase domain and catalytic site conserved with homologs in the known species. These results show that grass carp caspase8 has a structure similarity to teleost and mammalian caspase8 orthologs, and our study lay the theoretically foundation for further study of caspase8 function involving in apoptosis in grass carp.

show abstract

“…Constructs were added as indicated in figures. Assays of luciferase activity were done as described previously (16). HCT116 and HT29 cells expressing NF-kB reporter were grown to a subconfluent density and treated either with OXA, GYS32661, or with the combination of both.…”

Section: Nf-kb Luciferase Assaymentioning

confidence: 99%

RAC1b Overexpression Confers Resistance to Chemotherapy Treatment in Colorectal Cancer

Goka¹,

Chaturvedi²,

Lopez³

et al. 2019

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Resistance to chemotherapy represents a major limitation in the treatment of colorectal cancer. Novel strategies to circumvent resistance are critical to prolonging patient survival. Rac1b, a constitutively activated isoform of the small GTPase Rac1, is upregulated with disease progression and promotes cell proliferation and inhibits apoptosis by activation of NF-kB signaling. Here, we show that Rac1b overexpression correlates with cancer stage and confirmed Rac1b expression is associated with increased growth through enhancing NF-kB activity. Rac1b knockdown reduced cellular proliferation and reduced NF-kB activity. Surprisingly, Rac1b expression and NF-kB activity were upregulated in cells treated with chemotherapeutics, suggesting that Rac1b facilitates chemo-resistance through activation of NF-kB signaling. Knockdown of Rac1b or Rac inhibition increases the sensitivity of the cells to oxaliplatin. When used in combination, inhibition of Rac prevents the increase in NF-kB activity associated with chemotherapy treatment and increases the sensitivity of the cells to oxaliplatin. Although Rac inhibition or oxaliplatin treatment alone reduces the growth of colorectal cancer in vivo, combination therapy results in improved outcomes compared with single agents alone. We provide the first evidence that Rac1b expression confers resistance to chemotherapy in colorectal cancer. Additionally, we show that the use of a Rac inhibitor prevents chemoresistance by blocking activation of chemotherapy induced NF-kB signaling, providing a novel strategy to overcome resistance to chemotherapy in colorectal cancer.

show abstract

A dual role for Caspase8 and NF-κB interactions in regulating apoptosis and necroptosis of ovarian cancer, with correlation to patient survival

Cited by 34 publications

References 47 publications

Necroptotic cell death in anti‐cancer therapy

Necroptotic cell death in anti‐cancer therapy

Molecular Characterization of Caspase8 in Grass Carp (Ctenopharyngodon Idella)

RAC1b Overexpression Confers Resistance to Chemotherapy Treatment in Colorectal Cancer

Contact Info

Product

Resources

About