ArticleThe Journal of clinical investigation2018
Somatic mutation of the cohesin complex subunit confers therapeutic vulnerabilities in cancer.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 26 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
26 citing papers in PubMed, 37 citations in OpenAlex.
- The roles of chromatin remodeling and 3D genome organization in cancers: from mechanistic insights to emerging treatment options.Molecular cancer · 2026Review
- Cohesin mutations and chromatin changes in cancer.International journal of cancer · 2026Review
- Overcoming immune resistance in ovarian cancer: checkpoint inhibitors, tumor microenvironment, and translational advances.Frontiers in oncology · 2026Review
- Tumor-suppressive activities of SA1/STAG2 and effects of PARP impairment during brain development.Disease models & mechanisms · 2026Article
- S-phase PARylation of microprotein RSMC enhances the function of Sororin in sister chromatid cohesion.The EMBO journal · 2026Article
- Liquid-liquid phase separation: an emerging perspective on the tumorigenesis, progression, and treatment of tumors.Frontiers in immunology · 2025Review
- STAG2 loss in Ewing sarcoma alters enhancer-promoter contacts dependent and independent of EWS::FLI1.EMBO reports · 2024Article
- Synthetic Lethality between Cohesin and WNT Signaling Pathways in Diverse Cancer Contexts.Cells · 2024Article
- STAG2 Regulates Homologous Recombination Repair and Sensitivity to ATM Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Paralog-based synthetic lethality: rationales and applications.Frontiers in oncology · 2023Review
- Genetically induced redox stress occurs in a yeast model for Roberts syndrome.G3 (Bethesda, Md.) · 2022Article
- Prognostic Values and Underlying Regulatory Network of Cohesin Subunits in Esophageal Carcinoma.Journal of Cancer · 2022Article
- Paralogous synthetic lethality underlies genetic dependencies of the cancer-mutated geneLife science alliance · 2021Article
- The Cohesin Complex and Its Interplay with Non-Coding RNAs.Non-coding RNA · 2021Review
- Cohesin mutations in myeloid malignancies.Blood · 2021Review
- Cohesin Mutations in Cancer: Emerging Therapeutic Targets.International journal of molecular sciences · 2021Review
- STAG2 loss rewires oncogenic and developmental programs to promote metastasis in Ewing sarcoma.Cancer cell · 2021Article
- PDS5A and PDS5B in Cohesin Function and Human Disease.International journal of molecular sciences · 2021Review
- Combination of Talazoparib and Palbociclib as a Potent Treatment Strategy in Bladder Cancer.Journal of personalized medicine · 2021Article
- Article
Corrections and comments
- Retraction · 2026-01-16Falsification/Fabrication of Data · Investigation by Company/Institution · Misconduct - Official Investigation(s) and/or Finding(s) · Misconduct by Author · Objections by Author(s) ·
- Retracted
Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
Abstract
A synthetic lethality-based strategy has been developed to identify therapeutic targets in cancer harboring tumor-suppressor gene mutations, as exemplified by the effectiveness of poly ADP-ribose polymerase (PARP) inhibitors in BRCA1/2-mutated tumors. However, many synthetic lethal interactors are less reliable due to the fact that such genes usually do not perform fundamental or indispensable functions in the cell. Here, we developed an approach to identifying the "essential lethality" arising from these mutated/deleted essential genes, which are largely tolerated in cancer cells due to genetic redundancy. We uncovered the cohesion subunit SA1 as a putative synthetic-essential target in cancers carrying inactivating mutations of its paralog, SA2. In SA2-deficient Ewing sarcoma and bladder cancer, further depletion of SA1 profoundly and specifically suppressed cancer cell proliferation, survival, and tumorigenic potential. Mechanistically, inhibition of SA1 in the SA2-mutated cells led to premature chromatid separation, dramatic extension of mitotic duration, and consequently, lethal failure of cell division. More importantly, depletion of SA1 rendered those SA2-mutated cells more susceptible to DNA damage, especially double-strand breaks (DSBs), due to reduced functionality of DNA repair. Furthermore, inhibition of SA1 sensitized the SA2-deficient cancer cells to PARP inhibitors in vitro and in vivo, providing a potential therapeutic strategy for patients with SA2-deficient tumors.
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.