ArticleCancer discovery2022
SMYD3 Impedes Small Cell Lung Cancer Sensitivity to Alkylation Damage through RNF113A Methylation-Phosphorylation Cross-talk.
Article in Cancer discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 29 citations in OpenAlex.
- RNF113A Promotes Colorectal Cancer Metastasis by Regulating TGF-β Pathway and EMT via Ubiquitin-Mediated Degradation of SNIP1.Balkan medical journal · 2026Article
- A novel molecule ZYZ329 targeting histone methyltransferase SMYD3 suppresses pathological angiogenesis via the driven mitochondrial ROS/HIF-1α/VEGFA axis.Journal of translational medicine · 2026Article
- KDM7B-mediated demethylation of RNF113A regulates small cell lung cancer sensitivity to alkylation damage.bioRxiv : the preprint server for biology · 2026Article
- Dynamic Arginine Methylation of YBX1 Relay Controls Its Phase Separation and Chemoradiotherapy Resistance in Rectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Non-Histone Lysine Modifications in Tumor Microenvironment: Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Cancer network pharmacology: multi-network regulatory mechanisms and future directions.Medical oncology (Northwood, London, England) · 2025Review
- DNA damage response signatures are associated with frontline chemotherapy response and routes of tumor evolution in extensive stage small cell lung cancer.Molecular cancer · 2025Article
- SMYD family in cancer: epigenetic regulation and molecular mechanisms of cancer proliferation, metastasis, and drug resistance.Experimental & molecular medicine · 2024Review
- Targeting PRMT3 impairs methylation and oligomerization of HSP60 to boost anti-tumor immunity by activating cGAS/STING signaling.Nature communications · 2024Article
- Small Cell Lung Cancer-An Update on Chemotherapy Resistance.Current treatment options in oncology · 2024Review
- Review
- SMYD4 monomethylates PRMT5 and forms a positive feedback loop to promote hepatocellular carcinoma progression.Cancer science · 2024Article
- Cytoskeleton remodeling induced by SMYD2 methyltransferase drives breast cancer metastasis.Cell discovery · 2024Article
- SMYD3 promotes endometrial cancer through epigenetic regulation of LIG4/XRCC4/XLF complex in non-homologous end joining repair.Oncogenesis · 2024Article
- Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer.Frontiers in oncology · 2024Review
- Effect of RNF113A deficiency on oxidative stress-induced NRF2 pathway.Animal cells and systems · 2024Article
- Therapeutic targeting potential of the protein lysine and arginine methyltransferases to reverse cancer chemoresistance.Frontiers in molecular biosciences · 2024Review
- The SMYD3-MAP3K2 signaling axis promotes tumor aggressiveness and metastasis in prostate cancer.Science advances · 2023Article
- Histone lysine methyltransferase SMYD3 promotes oral squamous cell carcinoma tumorigenesis via H3K4me3-mediated HMGA2 transcription.Clinical epigenetics · 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
20 authors at 5 institutions in 3 countries.
Funding
Abstract
Small cell lung cancer (SCLC) is the most fatal form of lung cancer, with dismal survival, limited therapeutic options, and rapid development of chemoresistance. We identified the lysine methyltransferase SMYD3 as a major regulator of SCLC sensitivity to alkylation-based chemotherapy. RNF113A methylation by SMYD3 impairs its interaction with the phosphatase PP4, controlling its phosphorylation levels. This cross-talk between posttranslational modifications acts as a key switch in promoting and maintaining RNF113A E3 ligase activity, essential for its role in alkylation damage response. In turn, SMYD3 inhibition restores SCLC vulnerability to alkylating chemotherapy. Our study sheds light on a novel role of SMYD3 in cancer, uncovering this enzyme as a mediator of alkylation damage sensitivity and providing a rationale for small-molecule SMYD3 inhibition to improve responses to established chemotherapy. SIGNIFICANCE: SCLC rapidly becomes resistant to conventional chemotherapy, leaving patients with no alternative treatment options. Our data demonstrate that SMYD3 upregulation and RNF113A methylation in SCLC are key mechanisms that control the alkylation damage response. Notably, SMYD3 inhibition sensitizes cells to alkylating agents and promotes sustained SCLC response to chemotherapy. This article is highlighted in the In This Issue feature, p. 2007.
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.