ArticleNature medicine2016
Loss of cohesin complex components STAG2 or STAG3 confers resistance to BRAF inhibition in melanoma.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 89 citations in OpenAlex.
- mRNA Network: Solution for Tracking Chemotherapy Insensitivity in Small-Cell Lung Cancer.Journal of healthcare engineering · 2021Trial
- The roles of chromatin remodeling and 3D genome organization in cancers: from mechanistic insights to emerging treatment options.Molecular cancer · 2026Review
- BRAF inhibitor resistance in melanoma: from resistance mechanisms to therapeutic innovations.Molecular biomedicine · 2026Review
- Reduced STAG2 expression in myelodysplastic neoplasms and acute myeloid leukemia myelodysplasia-related: a potential biomarker associated with aneuploidy and disease progression.Frontiers in cell and developmental biology · 2026Article
- Dual-Specificity Protein Phosphatases Targeting Extracellular Signal-Regulated Kinases: Friends or Foes in the Biology of Cancer?International journal of molecular sciences · 2025Review
- Molecular Basis of BRAF Inhibitor Resistance in Melanoma: A Systematic Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Emerging roles of cohesin-STAG2 in cancer.Oncogene · 2025Review
- A STAG2-PAXIP1/PAGR1 axis suppresses lung tumorigenesis.The Journal of experimental medicine · 2025Article
- Adhesin Component Member STAG2 Enhances Cisplatin Tolerance in Colorectal Cancer Cells through the Epithelial-mesenchymal Transition Pathway.Recent patents on anti-cancer drug discovery · 2025Article
- Evolutionary dependency of cancer mutations in gene pairs inferred by nonsynonymous-synonymous mutation ratios.Genome medicine · 2024Article
- Review
- STAG2 inactivation reprograms glutamine metabolism of BRAF-mutant thyroid cancer cells.Cell death & disease · 2023Article
- Targeting RAS-RAF-MEK-ERK signaling pathway in human cancer: Current status in clinical trials.Genes & diseases · 2023Review
- CHK2 activation contributes to the development of oxaliplatin resistance in colorectal cancer.British journal of cancer · 2022Article
- Ectopic expression of meiotic cohesin generates chromosome instability in cancer cell line.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- A Whole-Genome CRISPR Screen Identifies AHR Loss as a Mechanism of Resistance to a PARP7 Inhibitor.Molecular cancer therapeutics · 2022Article
- STAG2 regulates interferon signaling in melanoma via enhancer loop reprogramming.Nature communications · 2022Article
- Plasticity of Extrachromosomal and Intrachromosomal BRAF Amplifications in Overcoming Targeted Therapy Dosage Challenges.Cancer discovery · 2022Article
- The multifaceted roles of cohesin in cancer.Journal of experimental & clinical cancer research : CR · 2022Review
- Melanocortin 1 receptor activation protects against alpha-synuclein pathologies in models of Parkinson's disease.Molecular neurodegeneration · 2022Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
The protein kinase B-Raf proto-oncogene, serine/threonine kinase (BRAF) is an oncogenic driver and therapeutic target in melanoma. Inhibitors of BRAF (BRAFi) have shown high response rates and extended survival in patients with melanoma who bear tumors that express mutations encoding BRAF proteins mutant at Val600, but a vast majority of these patients develop drug resistance. Here we show that loss of stromal antigen 2 (STAG2) or STAG3, which encode subunits of the cohesin complex, in melanoma cells results in resistance to BRAFi. We identified loss-of-function mutations in STAG2, as well as decreased expression of STAG2 or STAG3 proteins in several tumor samples from patients with acquired resistance to BRAFi and in BRAFi-resistant melanoma cell lines. Knockdown of STAG2 or STAG3 expression decreased sensitivity of BRAF(Val600Glu)-mutant melanoma cells and xenograft tumors to BRAFi. Loss of STAG2 inhibited CCCTC-binding-factor-mediated expression of dual specificity phosphatase 6 (DUSP6), leading to reactivation of mitogen-activated protein kinase (MAPK) signaling (via the MAPKs ERK1 and ERK2; hereafter referred to as ERK). Our studies unveil a previously unknown genetic mechanism of BRAFi resistance and provide new insights into the tumor suppressor function of STAG2 and STAG3.
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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.