SALL4, the missing link between stem cells, development and cancer

Tatetsu, Hiro; Kong, Nikki R.; Gao, Chong; Amabile, Giovanni; Tenen, Daniel G.; Chai, Li

doi:10.1016/j.gene.2016.02.019

Cited by 109 publications

(98 citation statements)

References 145 publications

(211 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…30 In AML, SALL4 directly interacts with β-catenin and induces the activation of Wnt/β-catenin signalling pathway, leading to the upregulation of the target genes of Wnt/β-catenin pathway including cyclin D1 and c-Myc. 7 CD44 is also suggested as a downstream target gene of Wnt/β-catenin signalling.…”

Section: Discussionmentioning

confidence: 99%

SALL4 promotes gastric cancer progression through activating CD44 expression

Yuan

Zhang

et al. 2016

Oncogenesis

View full text Add to dashboard Cite

The stem cell factor SALL4 (Sal-like protein 4) plays important roles in the development and progression of cancer. SALL4 is critically involved in tumour growth, metastasis and therapy resistance. However, the underlying mechanisms responsible for the oncogenic roles of SALL4 have not been well characterized. In this study, we demonstrated that SALL4 knockdown by short hairpin RNA greatly inhibited the proliferation, migration and invasion of gastric cancer cells. We further confirmed the inhibitory effects of SALL4 knockdown on gastric cancer cells by using a tetracycline-inducible system. Mechanistically, SALL4 knockdown downregulated the expression of CD44. The results of luciferase assay and chromatin immunoprecipitation study showed that SALL4 bound to CD44 promoter region and transcriptionally activated CD44. The results of rescue study revealed that CD44 overexpression antagonized SALL4 knockdown-mediated inhibition of gastric cancer cell proliferation, migration, and invasion in vitro and gastric cancer growth in vivo. Collectively, our findings indicate that SALL4 promotes gastric cancer progression through directly activating CD44 expression, which suggests a novel mechanism for the oncogenic roles of SALL4 in gastric cancer and represents a new target for gastric cancer therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

SALL4 promotes gastric cancer progression through activating CD44 expression

Yuan

Zhang

et al. 2016

Oncogenesis

View full text Add to dashboard Cite

show abstract

“…The transcription factor Sal‐like protein 4 (SALL4) is highly expressed in primordial germ cells, germ cells, early embryos, and embryonic stem cells (ESCs). It is critically involved in the self‐renewal and maintenance of pluripotency in ESCs 5 . Yuri, et al 6 demonstrated that SALL4 may be crucial for the lineage commitment in the inner cell mass cells and trophectoderm.…”

Section: Introductionmentioning

confidence: 99%

Differential expression of SALL4 in CTCs derived from hydatidiform moles and gestational trophoblastic neoplasms

Feng

Pei

et al. 2020

American J Rep Immunol

View full text Add to dashboard Cite

Problem To investigate EMT phenotype and SALL4 expression of circulating tumour cells (CTCs) in patients with gestational trophoblastic neoplasm (GTN). Method of study CanPatrol CTC detection system in combination with SALL4 RNA in situ hybridization was used to investigate the profile of CTCs in different types of gestational trophoblastic disease (GTD). Circulating CTCs were phenotyped and annotated with SALL4 expression in 41 GTD patients, including 12 HM and 29 GTN, as well as 22 pregnant volunteers. Results A positive correlation between the number of CTC and serum β‐hCG concentration was found among the GTN patients. The number of E/M‐CTC was positively correlated with serum β‐hCG, while M‐CTC was positively correlated with prognostic score. Comparison among malignant GTD, benign GTD and healthy pregnant women revealed a significant difference in the number of total CTC, E/M‐CTC, and M‐CTC but not in E‐CTC. ROC analysis was conducted to evaluate the performance of CTC phenotypes in distinguishing GTD patients from healthy pregnant women yielding an AUC as 0.826. Youden's index was maximal at the cutoff value of 8.5/4 mL with sensitivity and specificity at 53.66% and 100%, respectively. SALL4 expression was evaluated in GTD patients with CTC count greater than cutoff value. SALL4 high expressing CTCs (>2 signal dots) were detected in 66.67% (10/15) of malignant GTD patients but not in benign patients (0/5). Conclusion Differential expression of SALL4 was seen in CTCs derived from hydatidiform moles and GTN. CTC profiling may be developed as an adjunct marker to diagnose GTN.

show abstract

“…Therefore, to clarify the relationship between SALL4 and some of these factors would help to understand mechanisms that control the self-renewal and differentiation of piPSCs. Sall4 is vital for the maintenance of an undifferentiated state in both human and mouse ESCs [13] . Chromatin immunoprecipitation (ChIP) assays indicate that Sall4 binds to multiple loci in the genome, suggesting that Sall4 is a guardian of pluripotency that regulates many genes [7,11,14] .…”

Section: Introductionmentioning

confidence: 99%

SALL4 maintains self-renewal of porcine pluripotent stem cells through downregulation of OTX2

Wang¹,

Wang²,

Wang³

et al. 2019

Front. Agr. Sci. Eng.

View full text Add to dashboard Cite

Sall4 as one of the spalt family members contains several alternative splicing variants, which are differentially expressed and has a key role in maintaining pluripotent stem cells. However, the molecular features and function of SALL4 have not been well elucidated in porcine induced pluripotent stem cells (piPSCs). In this study, we identified SALL4 splice variants and found two SALL4 splicing variants through analysis of the porcine transcriptome data derived from piPSCs. SALL4A was only detected in piPSCs but SALL4B was globally expressed in porcine tissues and piPSCs. The level of SALL4B was significantly reduced when piPSCs differentiation occurred, however, the expression of SALL4A was not affected, indicating that SALL4B may be essential for the maintenance of piPSCs self-renewal. Overexpression of SALL4A and SALL4B in PEF cells could significantly stimulated expression of endogenous pluripotent genes, when SALL4B significantly promoted OCT4 expression. Conversely, SALL4A significantly promoted KLF4 expression. Additionally, both SALL4A and SALL4B could repress OTX2 promoter activity in a dose-dependent manner. Conversely, OTX2 also negatively regulated SALL4 expression. These observations indicate that a negative feedback regulatory mechanism may exist between SALL4 and OTX2, which is useful for the maintenance of the self-renewal of piPSCs.

show abstract

SALL4, the missing link between stem cells, development and cancer

Cited by 109 publications

References 145 publications

SALL4 promotes gastric cancer progression through activating CD44 expression

SALL4 promotes gastric cancer progression through activating CD44 expression

Differential expression of SALL4 in CTCs derived from hydatidiform moles and gestational trophoblastic neoplasms

SALL4 maintains self-renewal of porcine pluripotent stem cells through downregulation of OTX2

Contact Info

Product

Resources

About