ArticleProceedings of the National Academy of Sciences of the United States of America2018
Targeting cancer addiction for SALL4 by shifting its transcriptome with a pharmacologic peptide.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- SALL4 and microRNA: The Role of Let-7.Genes · 2021Pooled it
- Redistribution of super-enhancers promotes malignancy in human hepatocellular carcinoma.Journal of advanced research · 2026Article
- Peptide Drugs in Gastrointestinal Tumors: Integrating Targeting, Delivery, and Therapeutic Actions for Synergistic Strategies.Biomolecules · 2026Review
- PepLM-GNN: A graph neural network framework leveraging pre-trained language models for peptide-protein binding prediction.PLoS computational biology · 2026Article
- SALL4-targeted therapeutic peptide PEN-FFW suppresses PD-L1 and enhances CD8⁺ T cell cytotoxicity via regulating PI3K/AKT signaling in breast cancer.Immunologic research · 2026Article
- Neural crest induction requires SALL4-mediated BAF recruitment to lineage specific enhancers.Development (Cambridge, England) · 2025Article
- Article
- ACTH-like Peptides Compensate Rat Brain Gene Expression Profile Disrupted by Ischemia a Day After Experimental Stroke.Biomedicines · 2024Article
- Interpreting the molecular mechanisms of RBBP4/7 and their roles in human diseases (Review).International journal of molecular medicine · 2024Review
- Article
- The NuRD complex cooperates with SALL4 to orchestrate reprogramming.Nature communications · 2023Article
- The new advance of SALL4 in cancer: Function, regulation, and implication.Journal of clinical laboratory analysis · 2023Review
- Unveiling the molecular structure and role of RBBP4/7: implications for epigenetic regulation and cancer research.Frontiers in molecular biosciences · 2023Review
- Immunotherapy, targeted therapy, and their cross talks in hepatocellular carcinoma.Frontiers in immunology · 2023Review
- Article
- Role of SALL4 in HER2+ Breast Cancer Progression: Regulating PI3K/AKT Pathway.International journal of molecular sciences · 2022Article
- A transcriptional network of cell cycle dysregulation in noninvasive papillary urothelial carcinoma.Scientific reports · 2022Article
- Review
- DLX1 and the NuRD complex cooperate in enhancer decommissioning and transcriptional repression.Development (Cambridge, England) · 2022Article
- Carcinosarcoma of the stomach: four cases that expand the morphologic spectrum of gastric cancer with a primitive phenotype.Virchows Archiv : an international journal of pathology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 4 institutions in 2 countries.
Funding
Abstract
Sal-like 4 (SALL4) is a nuclear factor central to the maintenance of stem cell pluripotency and is a key component in hepatocellular carcinoma, a malignancy with no effective treatment. In cancer cells, SALL4 associates with nucleosome remodeling deacetylase (NuRD) to silence tumor-suppressor genes, such as PTEN. Here, we determined the crystal structure of an amino-terminal peptide of SALL4(1-12) complexed to RBBp4, the chaperone subunit of NuRD, at 2.7 Å, and subsequent design of a potent therapeutic SALL4 peptide (FFW) capable of antagonizing the SALL4-NURD interaction using systematic truncation and amino acid substitution studies. FFW peptide disruption of the SALL4-NuRD complex resulted in unidirectional up-regulation of transcripts, turning SALL4 from a dual transcription repressor-activator mode to singular transcription activator mode. We demonstrate that FFW has a target affinity of 23 nM, and displays significant antitumor effects, inhibiting tumor growth by 85% in xenograft mouse models. Using transcriptome and survival analysis, we discovered that the peptide inhibits the transcription-repressor function of SALL4 and causes massive up-regulation of transcripts that are beneficial to patient survival. This study supports the SALL4-NuRD complex as a drug target and FFW as a viable drug candidate, showcasing an effective strategy to accurately target oncogenes previously considered undruggable.
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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.