ArticleProtein & cell2022
Genome-wide CRISPR screen identifies synthetic lethality between DOCK1 inhibition and metformin in liver cancer.
Article in Protein & cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 46 citations in OpenAlex.
- Patient-Derived Organoid-Based CRISPR Screens in Cancer Research: Applications, Advances, and Challenges.Cancer medicine · 2026Review
- Rho GTPases in cancer resistance: mechanisms, vulnerabilities, and therapeutic opportunities.Biochemical Society transactions · 2026Review
- AMPK-activated BAP1 regulates pVHL stability and tumor-suppressive functions.Cell death and differentiation · 2026Article
- Multi-omics comprehensive analysis identified KIF22 and KRAS as highly synthetic lethal pairs for triple-negative breast cancer.Frontiers in oncology · 2026Article
- Survival outcomes of patients after liver transplantation for patients with hepatocellular carcinoma exceeding the Hangzhou criteria.Journal of gastrointestinal oncology · 2025Article
- Metformin Ameliorates Early Brain Injury After Subarachnoid Hemorrhage Via Improving Endoplasmic Reticulum Stress and Mitochondrial Stress-Mediated CaMolecular neurobiology · 2025Article
- Guanine Nucleotide Exchange Factors and Small GTPases: Their Regulation and Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- Association of metformin with risk of digestive tract cancers from a drug target mendelian randomization and cell experiments.Discover oncology · 2025Article
- Reconstructing the hepatocellular carcinoma microenvironment: the current status and challenges of 3D culture technology.Discover oncology · 2025Review
- Review
- Finding a needle in a haystack: functional screening for novel targets in cancer immunology and immunotherapies.Oncogene · 2025Review
- Advances in the Use of Metformin for Liver Disease.Current medicinal chemistry · 2025Review
- TBOPP, a DOCK1 Inhibitor, Potentiates Cisplatin Efficacy in Breast Cancer by Regulating Twist-mediated EMT.Current cancer drug targets · 2025Article
- Known and unknown: Exosome secretion in tumor microenvironment needs more exploration.Genes & diseases · 2025Review
- Transforming cancer treatment: integrating patient-derived organoids and CRISPR screening for precision medicine.Frontiers in pharmacology · 2025Review
- New use of an old drug: mechanism of oseltamivir phosphate inhibiting liver cancer through regulation of lipophagy via NEU1.Frontiers in pharmacology · 2025Article
- Article
- Single-cell multi-omics in the study of digestive system cancers.Computational and structural biotechnology journal · 2024Review
- GTF2H5 Identified as a crucial synthetic lethal target to counteract chemoresistance in colorectal cancer.Translational oncology · 2024Article
- Harnessing the evolving CRISPR/Cas9 for precision oncology.Journal of translational medicine · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
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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.