Sustained NF-κB-STAT3 signaling promotes resistance to Smac mimetics in Glioma stem-like cells but creates a vulnerability to EZH2 inhibition View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-12

AUTHORS

Cintia Carla da Hora, Kelsey Pinkham, Litia Carvalho, Max Zinter, Elie Tabet, Ichiro Nakano, Bakhos A. Tannous, Christian E. Badr

ABSTRACT

Glioblastoma is an incurable and highly aggressive brain tumor. Understanding therapeutic resistance and survival mechanisms driving this tumor type is key to finding effective therapies. Smac mimetics (SM) emerged as attractive cancer therapeutics particularly for tumor populations that are highly resistant to conventional apoptosis-inducing therapies. We evaluated the therapeutic efficacy of SM on Glioma stem-like cells (GSCs) and showed that this family of compounds stimulates an adaptive response triggered by TNFα. Increased expression of TNFα results in a prolonged and sustained activation of NF-κB and STAT3 signaling thus activating several tumor cell resistance mechanisms in GSCs. We show that STAT3 activation is contingent on EZH2 activation and uncover a synergistic lethality between SM and EZH2 inhibitors. Therapeutic inhibition of EZH2 impaired the viability of SM-treated GSCs. Our study outlines the molecular underpinnings of SM resistance in glioblastoma and provides mechanistic insight to overcome this resistance and increase therapeutic efficacy. More... »

PAGES

72

References to SciGraph publications

  • 2013-03. Identification of non-canonical NF-κB signaling as a critical mediator of Smac mimetic-stimulated migration and invasion of glioblastoma cells in CELL DEATH & DISEASE
  • 2012-06. A novel role for RIP1 kinase in mediating TNFα production in CELL DEATH & DISEASE
  • 2006-12. Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells in NATURE
  • 2008-11. IAPs contain an evolutionarily conserved ubiquitin-binding domain that regulates NF-κB as well as cell survival and oncogenesis in NATURE CELL BIOLOGY
  • 2014-02. Smac mimetics and innate immune stimuli synergize to promote tumor death in NATURE BIOTECHNOLOGY
  • 2000-10. Glial Fibrillary Acidic Protein: GFAP-Thirty-One Years (1969–2000) in NEUROCHEMICAL RESEARCH
  • 2006-12. Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma in MOLECULAR CANCER
  • 2009-05. Tumour necrosis factor and cancer in NATURE REVIEWS CANCER
  • 2017-02-15. Smac mimetics synergize with immune checkpoint inhibitors to promote tumour immunity against glioblastoma in NATURE COMMUNICATIONS
  • 2014-05. Smac mimetic promotes glioblastoma cancer stem-like cell differentiation by activating NF-κB in CELL DEATH & DIFFERENTIATION
  • 2016-04. BIRC3 is a novel driver of therapeutic resistance in Glioblastoma in SCIENTIFIC REPORTS
  • 2010-01. The transcriptional network for mesenchymal transformation of brain tumours in NATURE
  • 2015-10. NF-κB signaling in cancer stem cells: a promising therapeutic target? in CELLULAR ONCOLOGY
  • 2009-01. Is NF-κB a good target for cancer therapy? Hopes and pitfalls in NATURE REVIEWS DRUG DISCOVERY
  • 2009-10. Tumour-initiating cells: challenges and opportunities for anticancer drug discovery in NATURE REVIEWS DRUG DISCOVERY
  • 2010-08. IAPs: from caspase inhibitors to modulators of NF-κB, inflammation and cancer in NATURE REVIEWS CANCER
  • 1999-09. NF-κB activation by tumour necrosis factor requires the Akt serine–threonine kinase in NATURE
  • 2002-03. New functions for the matrix metalloproteinases in cancer progression in NATURE REVIEWS CANCER
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41420-019-0155-9

    DOI

    http://dx.doi.org/10.1038/s41420-019-0155-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1112506568

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30854231


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