ArticleMolecular cancer therapeutics2008
Caspase-, cathepsin-, and PERK-dependent regulation of MDA-7/IL-24-induced cell killing in primary human glioma cells.
Article in Molecular cancer therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 74 citations in OpenAlex.
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- Recent insights into apoptosis and toxic autophagy: The roles of MDA-7/IL-24, a multidimensional anti-cancer therapeutic.Seminars in cancer biology · 2020Review
- Mesenchymal stem cells derived from iPSCs expressing interleukin-24 inhibit the growth of melanoma in the tumor-bearing mouse model.Cancer cell international · 2020Article
- Target Therapy With Vaccinia Virus Harboring IL-24 For Human Breast Cancer.Journal of Cancer · 2020Article
- Inhibition of NR4A1 Promotes ROS Accumulation and IL24-Dependent Growth Arrest in Rhabdomyosarcoma.Molecular cancer research : MCR · 2019Article
- Interleukin-24 (IL24) Is Suppressed by PAX3-FOXO1 and Is a Novel Therapy for Rhabdomyosarcoma.Molecular cancer therapeutics · 2018Article
- Cancer terminator viruses (CTV): A better solution for viral-based therapy of cancer.Journal of cellular physiology · 2018Review
- eIF2α Phosphorylation Mediates IL24-Induced Apoptosis through Inhibition of Translation.Molecular cancer research : MCR · 2017Article
- Article
- Cryptococcus neoformans-induced macrophage lysosome damage crucially contributes to fungal virulence.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Melanoma differentiation-associated gene-7/interleukin-24 as a potential prognostic biomarker and second primary malignancy indicator in head and neck squamous cell carcinoma patients.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- Histone deacetylase inhibition synergistically enhances pemetrexed cytotoxicity through induction of apoptosis and autophagy in non-small cell lung cancer.Molecular cancer · 2014Article
- MDA-7/IL-24 inhibits Nrf2-mediated antioxidant response through activation of p38 pathway and inhibition of ERK pathway involved in cancer cell apoptosis.Cancer gene therapy · 2014Article
- MDA-7/IL-24: multifunctional cancer killing cytokine.Advances in experimental medicine and biology · 2014Review
- Molecular targets and signaling pathways regulated by interleukin (IL)-24 in mediating its antitumor activities.Journal of molecular signaling · 2013Article
- Combining histone deacetylase inhibitors with MDA-7/IL-24 enhances killing of renal carcinoma cells.Cancer biology & therapy · 2013Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
Abstract
Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) is a novel cytokine displaying selective apoptosis-inducing activity in transformed cells without harming normal cells. The present studies focused on defining the mechanism(s) by which a GST-MDA-7 fusion protein inhibits cell survival of primary human glioma cells in vitro. GST-MDA-7 killed glioma cells with diverse genetic characteristics that correlated with inactivation of ERK1/2 and activation of JNK1-3. Activation of JNK1-3 was dependent on protein kinase R-like endoplasmic reticulum kinase (PERK), and GST-MDA-7 lethality was suppressed in PERK-/- cells. JNK1-3 signaling activated BAX, whereas inhibition of JNK1-3, deletion of BAX, or expression of dominant-negative caspase-9 suppressed lethality. GST-MDA-7 also promoted a PERK-, JNK-, and cathepsin B-dependent cleavage of BID; loss of BID function promoted survival. GST-MDA-7 suppressed BAD and BIM phosphorylation and heat shock protein 70 (HSP70) expression. GST-MDA-7 caused PERK-dependent vacuolization of LC3-expressing endosomes whose formation was suppressed by incubation with 3-methyladenine, expression of HSP70 or BiP/GRP78, or knockdown of ATG5 or Beclin-1 expression but not by inhibition of the JNK1-3 pathway. Knockdown of ATG5 or Beclin-1 expression or overexpression of HSP70 reduced GST-MDA-7 lethality. Our data show that GST-MDA-7 induces an endoplasmic reticulum stress response that is causal in the activation of multiple proapoptotic pathways, which converge on the mitochondrion and highlight the complexity of signaling pathways altered by mda-7/IL-24 in glioma cells that ultimately culminate in decreased tumor cell survival.
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