ArticleJournal of translational medicine2017
IRE1α-XBP1 pathway promotes melanoma progression by regulating IL-6/STAT3 signaling.
Article in Journal of translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 69 citations in OpenAlex.
- XBP1 signaling from tumor metabolic stress to myeloid driven immunotherapy resistance (Review).International journal of molecular medicine · 2026Review
- Blockade of IRE1-XBP1 Signaling Pathway Ameliorates IL-6-dependent Nerve Damage and Neuron Pyroptosis after Subarachnoid Hemorrhage in Mice.Experimental neurobiology · 2026Article
- Endoplasmic reticulum stress promotes colorectal cancer proliferation by regulating autophagy via XBP1s.Translational cancer research · 2026Article
- Multifunctional nanotherapeutics for targeted modulation of endoplasmic reticulum stress to potentiate cancer therapy.Asian journal of pharmaceutical sciences · 2026Review
- The canonical ER stress IRE1α/XBP1 pathway mediates skeletal muscle wasting during pancreatic cancer cachexia.EMBO molecular medicine · 2025Article
- XBP1 Knockdown Alleviates Pyroptosis and Promotes Th17/Treg Imbalance in Periodontitis by Inhibiting the IL-17 Signaling Pathway.Inflammation · 2025Article
- Modulation of Endoplasmic Reticulum Stress in Experimental Anti-Cancer Therapy.International journal of molecular sciences · 2025Review
- Review
- Integration of Network Pharmacology, Molecular Docking, and Experimental Validation to Identify the Effect of EGCG on Alleviating Chondrocyte Inflammatory Damage by Targeting ER Stress-STAT3 Crosstalk.Journal of inflammation research · 2025Article
- Endoplasmic Reticulum Stress in Cancer Progression: A Comprehensive Review of Its Role and Mechanisms.International journal of medical sciences · 2025Review
- Inhibition of IRE1α/XBP1 axis alleviates LPS-induced acute lung injury by suppressing TXNIP/NLRP3 inflammasome activation and ERK/p65 signaling pathway.Respiratory research · 2024Article
- UPF3B modulates endoplasmic reticulum stress through interaction with inositol-requiring enzyme-1α.Cell death & disease · 2024Article
- Endoplasmic reticulum stress-a key guardian in cancer.Cell death discovery · 2024Review
- Endoplasmic reticular stress as an emerging therapeutic target for chronic pain: a narrative review.British journal of anaesthesia · 2024Review
- Endoplasmic reticulum stress and the unfolded protein response: emerging regulators in progression of traumatic brain injury.Cell death & disease · 2024Review
- Tumorous IRE1α facilitates CD8Cell communication and signaling : CCS · 2024Article
- Machine learning-based identification of an immunotherapy-related signature to enhance outcomes and immunotherapy responses in melanoma.Frontiers in immunology · 2024Article
- Control of immune cell function by the unfolded protein response.Nature reviews. Immunology · 2023Review
- Targeting XBP1 mRNA splicing sensitizes glioblastoma to chemotherapy.FASEB bioAdvances · 2023Article
- Bromodomain-containing Protein 4 Regulates Innate Inflammation in Airway Epithelial Cells via Modulation of Alternative Splicing.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe IRE1α-XBP1 pathway is the most conserved branch of the unfolded protein response pathways, which are activated during endoplasmic reticulum (ER) stress caused by the accumulation of unfolded/misfolded proteins in the ER lumen. The IRE1α-XBP1 pathway plays a critical role in various cancers. However, the role of this pathway in melanoma cell growth remains unclear.
methodsSixty-one pairs of melanoma specimens and corresponding normal tissues from patients were stained with XBP1. Then, XBP1 splicing levels were detected in human tissues and cell lines at the mRNA level. IL-6 expression levels were determined in both melanocytes (HEMn-MP) and melanoma cells (Mel-RMu) overexpressing the spliced form of XBP1 (XBP1s). IL-6 expression was also examined in 4μ8C-treated HEMn-MP and Mel-RMu cells overexpressing IRE1α. Next, we analyzed potential XBP1s binding sites within the IL-6 promoter and conducted ChIP experiments. IL-6/STAT3 signaling was detected by western blotting. Melanoma cell proliferation was examined by CCK8 and BrdU assays.
resultsThe mRNA and protein expression levels of XBP1s were significantly elevated in human melanoma tissues and cell lines compared with normal tissues or melanocytes, thus indicating the activation of the IRE1α-XBP1 branch in melanoma. Ectopic expression of IRE1α or XBP1s robustly enhanced IL-6 expression in HEMn-MP and Mel-RMu cells. Moreover, the inhibition of the RNase activity of IRE1α also abolished the effect of IRE1α in promoting IL-6 expression. Mechanistically, XBP1 binds the IL-6 promoter and activates its expression. Furthermore, secreted IL-6 functions in an autocrine/paracrine manner, activates the intracellular JAK/STAT3 pathway and promotes the proliferation of melanoma cells.
conclusionOur results reveal that the IRE1α-XBP1 pathway regulates Mel-RMu cell proliferation and progression by activating IL-6/STAT3 signaling.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.