ArticleCell death discovery2021
RCN1 induces sorafenib resistance and malignancy in hepatocellular carcinoma by activating c-MYC signaling via the IRE1α-XBP1s pathway.
Article in Cell death discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The trial behind it
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Who cites it
27 citing papers in PubMed, 50 citations in OpenAlex.
- Comprehensive study of the tumor immune microenvironment and the prognostic significance of reticulocalbin-1: a pan-cancer analysis.Functional & integrative genomics · 2026Article
- Ubiquitination-Related Diagnostic Biomarkers for Diabetic Nephropathy: Insights From Multiomic Analysis, Drug Docking, and Experimental Validation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Epigenetic Mechanisms Involved in Hcv Infection and Human HCC.International journal of molecular sciences · 2025Review
- TMEM166 negatively regulates unfolded protein response to affect hepatocellular carcinoma cell growth and sorafenib resistance.Cell death & disease · 2025Article
- RCN3 functions as a tumor promoter in colorectal cancer by modulating the GRP78-PI3K-AKT signaling pathway.Oncogene · 2025Article
- Reticulocalbin-1 in clear cell renal cell carcinoma: clinical and functional evidence for its role as a biomarker and potential therapeutic target.BMC cancer · 2025Article
- RCN1 downregulation-driven endoplasmic reticulum stress impairs endothelial function and diabetic foot ulcer healing.Cellular and molecular life sciences : CMLS · 2025Article
- Role of miR-26b in regulating non-small cell lung cancer progression via targeting RCN1.Journal of thoracic disease · 2025Article
- Sorafenib-loaded metal-organic framework nanoparticles for anti-hepatocellular carcinoma effects through synergistically potentiating ferroptosis and remodeling tumor immune microenvironment.Materials today. Bio · 2025Article
- TTC36 promotes proliferation and drug resistance in hepatocellular carcinoma cells by inhibiting c-Myc degradation.Cell death & disease · 2025Article
- ALKBH5 Inhibits YTHDF2-m6A-Mediated Degradation of RCN1 mRNA to Promote Keloid Formation by Activating IRE1α-XBP1-Mediated ER Stress.Journal of cosmetic dermatology · 2025Article
- Endoplasmic Reticulum Stress: Triggers Microenvironmental Regulation and Drives Tumor Evolution.Cancer medicine · 2025Review
- Transcriptome-based network analysis related to regulatory T cells infiltration identified RCN1 as a potential biomarker for prognosis in clear cell renal cell carcinoma.BioData mining · 2024Article
- Targeted transcriptional downregulation of MYC using epigenomic controllers demonstrates antitumor activity in hepatocellular carcinoma models.Nature communications · 2024Article
- AFP-HSP90 mediated MYC/MET activation promotes tumor progression in hepatocellular carcinoma and gastric cancers.Cancer cell international · 2024Article
- Semaphorin 3C (Sema3C) reshapes stromal microenvironment to promote hepatocellular carcinoma progression.Signal transduction and targeted therapy · 2024Article
- An integrated investigation of sulfotransferases (SULTs) in hepatocellular carcinoma and identification of the role of SULT2A1 on stemness.Apoptosis : an international journal on programmed cell death · 2024Article
- Oxyberberine sensitizes liver cancer cells to sorafenib via inhibiting NOTCH1-USP7-c-Myc pathway.Hepatology communications · 2024Article
- Systematic integration of molecular and clinical approaches in HCV-induced hepatocellular carcinoma.Journal of translational medicine · 2024Article
- Advances in hepatocellular carcinoma drug resistance models.Frontiers in medicine · 2024Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The increasing incidence of hepatocellular carcinoma (HCC) is of great concern globally, but the molecular pathogenesis of these tumors remains unclear. Sorafenib is a first-line drug for the treatment of advanced HCC. However, the efficacy of sorafenib in improving patient survival is limited, and most patients inevitably develop resistance to this drug. Recent studies have demonstrated that the activation of the IRE1α-XBP1s pathway might play a protective role in the response to sorafenib and contribute to malignancy in HCC. Here, we found that RCN1, an endoplasmic reticulum resident protein, is significantly upregulated in sorafenib-resistant HCC cells and promotes tumor progression. Our analysis showed that RCN1 may be an independent predictor of tumor recurrence and overall survival. Mechanistically, RCN1 promotes the dissociation of GRP78 from IRE1α in sorafenib-resistant cells by interacting with GRP78 through its EFh1/2 domain. Subsequently, the IRE1α-XBP1s pathway, a branch of the unfolded protein response, is sustainably activated. Interestingly, IRE1α-XBP1s pathway activity is required for c-MYC signaling, one of the most highly activated oncogenic pathways in HCC. These results suggest that RCN1-targeted therapy might be a feasible strategy for the treatment of HCC.
Identifiers
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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.