ArticleBMC cancer2021
Pooled CRISPR screening in pancreatic cancer cells implicates co-repressor complexes as a cause of multiple drug resistance via regulation of epithelial-to-mesenchymal transition.
Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- TRIM32-mediated ABI2 downregulation promotes anoikis resistance and metastasis by regulating EMT in lung adenocarcinoma.Cellular and molecular life sciences : CMLS · 2026Article
- A tumor microenvironment-focused signature based on m6A and lactylation modification predicts prognosis and immunotherapy response in hepatocellular carcinoma.Discover oncology · 2026Article
- Identification of HSPE1 as a new actionable cancer vulnerability leads to an innovative and effective combination therapy for pancreatic ductal adenocarcinoma.Molecular cancer · 2026Article
- Epigenetic and transcriptional control of classical and basal-like cell states in pancreatic ductal adenocarcinoma.Gastroenterology report · 2026Review
- CRISPR Technology in Disease Management: An Updated Review of Clinical Translation and Therapeutic Potential.Cell proliferation · 2025Article
- CRISPR/Cas technologies in pancreatic cancer research and therapeutics: recent advances and future outlook.Discover oncology · 2025Review
- KRAS inhibition reverses chemotherapy resistance promoted by therapy-induced senescence-like in pancreatic ductal adenocarcinoma.Translational oncology · 2025Article
- Co-essentiality analysis identifies PRR12 as a cohesin interacting protein and contributor to genomic integrity.Developmental cell · 2025Article
- Functional genomics reveals an off-target dependency of drug synergy in gastric cancer therapy.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Article
- Cancer Stem Cells: Current Challenges and Future Perspectives.Methods in molecular biology (Clifton, N.J.) · 2024Review
- Epigenetic control of pancreatic cancer metastasis.Cancer metastasis reviews · 2023Review
- Genomic analysis reveals HDAC1 regulates clinically relevant transcriptional programs in Pancreatic cancer.BMC cancer · 2023Article
- Functional genomics reveals an off-target dependency of drug synergy in gastric cancer therapy.bioRxiv : the preprint server for biology · 2023Article
- Dampening HOTAIR sensitizes the gastric cancer cells to oxaliplatin through miR-195-5p and ABCG2 pathway.Journal of cellular and molecular medicine · 2023Article
- Multi-Omics Analysis of NCI-60 Cell Line Data Reveals Novel Metabolic Processes Linked with Resistance to Alkylating Anti-Cancer Agents.International journal of molecular sciences · 2023Article
- A small Rho GTPase RAB25 with a potential role in chemotherapy resistance in pancreatic cancer.Cancer biomarkers : section A of Disease markers · 2023Article
- Genome-wide CRISPR/Cas9 screening for drug resistance in tumors.Frontiers in pharmacology · 2023Review
- Review
- ABI2-mediated MEOX2/KLF4-NANOG axis promotes liver cancer stem cell and drives tumour recurrence.Liver international : official journal of the International Association for the Study of the Liver · 2022Article
- Pre-clinical Models of Metastasis in Pancreatic Cancer.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPancreatic ductal adenocarcinoma (PDAC) patients suffer poor outcomes, including a five-year survival of below 10%. Poor outcomes result in part from therapeutic resistance that limits the impact of cytotoxic first-line therapy. Novel therapeutic approaches are needed, but currently no targeted therapies exist to treat PDAC.
methodsTo assess cellular resistance mechanisms common to four cytotoxic chemotherapies (gemcitabine, 5-fluorouracil, irinotecan, and oxaliplatin) used to treat PDAC patients, we performed four genome-wide CRISPR activation (CRISPR
resultsOur data revealed activation of ABCG2, a well-described efflux pump, as the most consistent mediator of resistance in each of our screens. CRISPR-mediated activation of genes involved in transcriptional co-repressor complexes also conferred resistance to multiple drugs. Expression of many of these genes, including HDAC1, is associated with reduced survival in PDAC patients. Up-regulation of HDAC1 in vitro increased promoter occupancy and expression of several genes involved in the epithelial-to-mesenchymal transition (EMT). These cells also displayed phenotypic changes in cellular migration consistent with activation of the EMT pathway. The expression changes resulting from HDAC1 activation were also observed with activation of several other co-repressor complex members. Finally, we developed a publicly available analysis tool, PancDS, which integrates gene expression profiles with our screen results to predict drug sensitivity in resected PDAC tumors and cell lines.
conclusionOur results provide a comprehensive resource for identifying cellular mechanisms of drug resistance in PDAC, mechanistically implicate HDAC1, and co-repressor complex members broadly, in multi-drug resistance, and provide an analytical tool for predicting treatment response in PDAC tumors and cell lines.
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