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SALL4, the missing link between stem cells, development and cancer
Open accessAbstract
There is a growing body of evidence supporting that cancer cells share many similarities with embryonic stem cells (ESCs). For example, aggressive cancers and ESCs share a common gene expression signature that includes hundreds of genes. Since ESC genes are not present in most adult tissues, they could be ideal candidate targets for cancer-specific diagnosis and treatment. This is an exciting cancer-targeting model. The major hurdle to test this model is to identify the key factors/pathway(s) within ESCs that are responsible for the cancer phenotype. SALL4 is one of few genes that can establish this link. The first publication of SALL4 is on its mutation in a human inherited disorder with multiple developmental defects. Since then, over 300 papers have been published on various aspects of this gene in stem cells, development, and cancers. This review aims to summarize our current knowledge of SALL4, including a SALL4-based approach to classify and target cancers. Many questions about this important gene still remain unanswered, specifically, on how this gene regulates cell fates at a molecular level. Understanding SALL4's molecular functions will allow development of specific targeted approaches in the future.
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“As a transcription factor, the uniqueness of SALL4 lies in the fact that it is expressed in embryonic cells, downregulated during development, absent in most adult tissues, and re-expressed in a significant fraction of almost all human adult tumors (Moein et al, 2022; Tatetsu et al, 2016).”
From Targeting transcription factors through an IMiD independent zinc finger domain (2025) · cites this paper as Tatetsu et al, 2016
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“Mostly, the re-expression of SALL4 was associated with increased tumor cell proliferation and decreased patient survival.”
From Epigenetic control of melanoma cell invasiveness by the stem cell factor SALL4 (2021) · cites this paper as [26]
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“As a transcription factor, the uniqueness of SALL4 lies in the fact that it is expressed in embryonic cells, downregulated during development, absent in most adult tissues, and re-expressed in a significant fraction of almost all human adult tumors (Moein et al, 2022; Tatetsu et al, 2016).”
From Targeting transcription factors through an IMiD independent zinc finger domain (2025) · cites this paper as Tatetsu et al, 2016
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“its aberrant re-expression has been reported for an increasing number of cancer types, such as germ cell tumors, hepatocellular carcinoma, gastric cancer, leukemia-, and others26”
From Epigenetic control of melanoma cell invasiveness by the stem cell factor SALL4 (2021) · cites this paper as [26]
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“Of note, Sall4 is crucial for the early development of embryos, and mice without Sall4 cannot survive beyond E6.540–42.”
From The NuRD complex cooperates with SALL4 to orchestrate reprogramming (2023) · cites this paper as [40]
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Self-citationDynamics of repair and regeneration of adult zebrafish respiratory gill tissue after cryoinjuryPreprint
Ramel, M., Progatzky, F., Rýdlová, A., Wane, M., Schymeinsky, J., Williams, C. M. M., Jung, B., Lamb, J. R., Thomas, M. J., Bugeon, L., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.05.27.445469 · Cited by 4
Targeting transcription factors through an IMiD independent zinc finger domain
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“As a transcription factor, the uniqueness of SALL4 lies in the fact that it is expressed in embryonic cells, downregulated during development, absent in most adult tissues, and re-expressed in a signi fi cant fraction of almost all human adult tumors (Moein et al, 2022; Tatetsu et al, 2016).”
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Xu, D., Feng, F., Pei, Y., Zhang, Y., Wu, Y., Guo, Y. C., & Cui, W. (2020) · American Journal of Reproductive Immunology · doi:10.1111/aji.13233 · Cited by 4
Kawakami, H., Chen, K. Q., Zhang, R., Pappas, M. P., Bailey, A., Reisz, J. A., Corcoran, D., Nishinakamura, R., D’Alessandro, A., & Kawakami, Y. (2023) · Developmental Biology · doi:10.1016/j.ydbio.2023.06.004 · Cited by 5
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Stipoljev, F., Miric-Tesanic, D., Hafner, T., Barbalić, M., Logara, M., Lasan-Trčić, R., Vičić, A., & Juraški, R. G. (2017) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2017.08.010 · Cited by 4
Farawela, H. M., Zawam, H. M., Al-Wakeel, H. A., El-Nagdy, M. H., Elrefaey, F. A., & Abdel-Rahman, H. A. (2019) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365513.2018.1555854 · Cited by 6
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SALL4 as a Useful Marker for the Distinction of Various Gestational Trophoblastic Disease Subtypes
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CELLoGeNe - An energy landscape framework for logical networks controlling cell decisions
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Lakpour, N., Ghods, R., Abolhasani, M., Zanjani, L. S., Saliminejad, K., Kalantari, E., Saki, S., Ranjbar, M. M., Balay‐Goli, L., Sadeghi, M. R., et al. (2024) · Biomarkers · doi:10.1080/1354750x.2024.2361796 · Cited by 3
Demethylation and upregulation of an oncogene post hypomethylating treatmentPreprint
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The KRAB-Zinc Finger protein ZKSCAN3 represses enhancers via embedded retrotransposonsPreprint
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Neural crest induction requires SALL4-mediated BAF recruitment to lineage specific enhancers
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Role of Transcription Factor BEND3 and Its Potential Effect on Cancer Progression
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A Clinical Guidance for the Management of Patients With Hepatoid Adenocarcinoma and A Case Series
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Metadata
- Authors
- Tatetsu, H., Kong, N. R., Chong, G., Amabile, G., Tenen, D. G., & Chai, L.
- Affiliations
- Brigham and Women's Hospital (US)
- Adienne (Switzerland) (CH)
- Harvard University (US)
- Corresponding author
- Chai, Li
- Venue
- Gene
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 584
- Issue
- 2
- Pages
- 111-119
- ISSN
- 0378-1119 (ISSN-L)
- PMC
- PMC4823161
- OpenAlex
- W2274155363
- Cited by
- 130
- References
- 152
- Citations by year
- 2026: 5 · 2025: 15 · 2024: 9 · 2023: 20 · 2022: 12 · 2021: 24 · 2020: 13 · 2019: 9 · 2018: 11 · 2017: 8 · 2016: 3
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Gene (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (GM089820, P01HL095489, R03CA184531)
- Ministry of Education - Singapore
- V Foundation for Cancer Research
- Leukemia and Lymphoma Society (SLP-8004-14, TRP-6482-16)
- National Research Foundation
- National Medical Research Council
- Ministry of Health -Singapore
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- SALL4, embryonic stem cells, cancer stem cells, carcinogenesis, cancer classification, targeted cancer therapy, cell fate regulation, developmental defects, gene expression signatures
- MeSH terms
- Humans, Neoplasms, Stem Cells, Transcription Factors
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