ArticleMolecular cancer research : MCR2016
JNK1 Inhibition Attenuates Hypoxia-Induced Autophagy and Sensitizes to Chemotherapy.
Article in Molecular cancer research : MCR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Small-molecule autophagy modulators: Mechanisms, therapeutic potential, and development challenges in pathological settings.Fundamental research · 2026Review
- Potential Mechanisms of MAP Kinase JNK's Involvement in Modulating Cancer Cell Fate in a Cisplatin Concentration-Dependent Manner.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Review
- A Novel Platinum Resistance-Related Immune Gene Signature for Overall Survival Prediction in Patients with Ovarian Cancer.Biochemical genetics · 2024Article
- NETISCE: a network-based tool for cell fate reprogramming.NPJ systems biology and applications · 2022Article
- Strategies for Improving Photodynamic Therapy Through Pharmacological Modulation of the Immediate Early Stress Response.Methods in molecular biology (Clifton, N.J.) · 2022Review
- Inhibiting Cytoprotective Autophagy in Cancer Therapy: An Update on Pharmacological Small-Molecule Compounds.Frontiers in pharmacology · 2022Review
- Identification of Senescence-Related Subtypes, the Development of a Prognosis Model, and Characterization of Immune Infiltration and Gut Microbiota in Colorectal Cancer.Frontiers in medicine · 2022Article
- Unfolding the role of autophagy in the cancer metabolism.Biochemistry and biophysics reports · 2021Article
- Inhibition of the sonic hedgehog pathway activates TGF-β-activated kinase (TAK1) to induce autophagy and suppress apoptosis in thyroid tumor cells.Cell death & disease · 2021Article
- JNK in Tumor Microenvironment: Present Findings and Challenges in Clinical Translation.Cancers · 2021Review
- Vaccinia-related kinase 2 blunts sorafenib's efficacy against hepatocellular carcinoma by disturbing the apoptosis-autophagy balance.Oncogene · 2021Article
- Autophagy is a double-edged sword in the therapy of colorectal cancer.Oncology letters · 2021Review
- Size-controlled human adipose-derived stem cell spheroids hybridized with single-segmented nanofibers and their effect on viability and stem cell differentiation.Biomaterials research · 2021Article
- Review
- Review
- Targeting autophagy-related protein kinases for potential therapeutic purpose.Acta pharmaceutica Sinica. B · 2020Review
- A risk signature with four autophagy-related genes for predicting survival of glioblastoma multiforme.Journal of cellular and molecular medicine · 2020Article
- Autophagy in cancer: moving from understanding mechanism to improving therapy responses in patients.Cell death and differentiation · 2020Review
- Resumption of Autophagy by Ubisol-QOxidative medicine and cellular longevity · 2019Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledInhibition of hypoxia-induced stress signaling through JNK potentiates the effects of oxaliplatin. The JNK pathway plays a role in both autophagy and apoptosis; therefore, it was determined how much of the effect of JNK inhibition on oxaliplatin sensitivity is dependent on its effect on autophagy. We studied the impact of JNK isoform downregulation in the HT29 colon adenocarcinoma cell line on hypoxia- and oxaliplatin-induced responses. Electron microscopic analyses demonstrated that both oxaliplatin- and hypoxia-induced formations of autophagosomes were reduced significantly in HT29 cells treated with the JNK inhibitor SP600125. The role of specific JNK isoforms was defined using HT29-derived cell lines stably expressing dominant-negative constructs for JNK1 and JNK2 (HTJ1.3 and HTJ2.2, respectively). These cell lines demonstrated that functional JNK1 is required for hypoxia-induced autophagy and that JNK2 does not substitute for it. Inhibition of autophagy in HTJ1.3 cells also coincided with enhancement of intrinsic apoptosis. Analysis of Bcl2-family proteins revealed hyperphosphorylation of Bcl-XL in the HTJ1.3 cell line, but this did not lead to the expected dissociation from Beclin 1. Consistent with this, knockdown of Bcl-XL in HT29 cells did not significantly affect the induction of autophagy, but abrogated hypoxic resistance to oxaliplatin due to the faster and more robust activation of apoptosis. IMPLICATIONS: These data suggest that balance between autophagy and apoptosis is shifted toward apoptosis by downregulation of JNK1, contributing to oxaliplatin sensitization. These findings further support the investigation of JNK inhibition in colorectal cancer treatment. Mol Cancer Res; 14(8); 753-63. ©2016 AACR.
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