SALL4 Oncogenic Function in Cancers: Mechanisms and Therapeutic Relevance

Sun, Boshu; Xu, Liangliang; Bi, Wenhui; Ou, Wen‐Bin

doi:10.3390/ijms23042053

Cited by 28 publications

(34 citation statements)

References 211 publications

(284 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In recent years molecular targeted therapy for cancer has attracted a great deal of attention in order to achieve the goals of precision medicine. The functional association of SALL4 with cancer incidence, progression, and metastasis suggests that SALL4-targeting could be effective in eradicating cancer cells [ 85 ]. However, transcription factors (TFs) historically have been viewed to be “undrugable”, and multiple issues should be considered in designing efficient therapeutics.…”

Section: Sall4 As a Potential Therapeutic Targetmentioning

confidence: 99%

SALL4: An Intriguing Therapeutic Target in Cancer Treatment

Moein

Tenen

Amabile

et al. 2022

Cells

View full text Add to dashboard Cite

Spalt-Like Transcription Factor 4 (SALL4) is a critical factor for self-renewal ability and pluripotency of stem cells. On the other hand, various reports show tight relation of SALL4 to cancer occurrence and metastasis. SALL4 exerts its effects not only by inducing gene expression but also repressing a large cluster of genes through interaction with various epigenetic modifiers. Due to high expression of SALL4 in cancer cells and its silence in almost all adult tissues, it is an ideal target for cancer therapy. However, targeting SALL4 meets various challenges. SALL4 is a transcription factor and designing appropriate drug to inhibit this intra-nucleus component is challenging. On the other hand, due to lack of our knowledge on structure of the protein and the suitable active sites, it becomes more difficult to reach the appropriate drugs against SALL4. In this review, we have focused on approaches applied yet to target this oncogene and discuss the potential of degrader systems as new therapeutics to target oncogenes.

show abstract

Section: Sall4 As a Potential Therapeutic Targetmentioning

confidence: 99%

SALL4: An Intriguing Therapeutic Target in Cancer Treatment

Moein

Tenen

Amabile

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…Any abnormal expression or mutation in this gene leads to the progression of various diseases and the development of different cancers [ 10 ]. In recent years, SALL4 has emerged as a potential biomarker in many cancers, including BC [ 11 , 12 , 13 , 14 ]. Researchers have observed that 86.1% of BC cases have shown high SALL4 expression, and it is regulating different tumor suppressor genes, including E-cadherin (CDH1) and PTEN [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Role of SALL4 in HER2+ Breast Cancer Progression: Regulating PI3K/AKT Pathway

Pattanayak

Lameirinhas

Torres-Ruiz

et al. 2022

IJMS

View full text Add to dashboard Cite

Treatment for the HER2+ breast cancer subtype is still unsatisfactory, despite breakthroughs in research. The discovery of various new molecular mechanisms of transcription factors may help to make treatment regimens more effective. The transcription factor SALL4 has been related to aggressiveness and resistance therapy in cancer. Its molecular mechanisms and involvement in various signaling pathways are unknown in the HER2+ breast cancer subtype. In this study, we have evaluated the implication of SALL4 in the HER2+ subtype through its expression in patients’ samples and gain and loss of function in HER2+ cell lines. We found higher SALL4 expression in breast cancer tissues compared to healthy tissue. Interestingly, high SALL4 expression was associated with disease relapse and poor patient survival. In HER2+ cell lines, transient overexpression of SALL4 modulates PI3K/AKT signaling through regulating PTEN expression and BCL2, which increases cell survival and proliferation while reducing the efficacy of trastuzumab. SALL4 has also been observed to regulate the epithelial–mesenchymal transition and stemness features. SALL4 overexpression significantly reduced the epithelial markers E-cadherin, while it increased the mesenchymal markers β-catenin, vimentin and fibronectin. Furthermore, it has been also observed an increased expression of MYC, an essential transcription factor for regulating epithelial-mesenchymal transition and/or cancer stem cells. Our study demonstrates, for the first time, the importance of SALL4 in the HER2+ subtype and partial regulation of trastuzumab sensitivity. It provides a viable molecular mechanism-driven therapeutic strategy for an important subset of HER2-overexpressing patients whose malignancies are mediated by SALL4 expression.

show abstract

“…Salt‐like transcription factor 4 (SALL4) is a regulator of embryonic stem cells involved in self‐renewal and pluripotency 5 . SALL4 is a novel cancer target, 6 and has been studied in different tumors.…”

Section: Introductionmentioning

confidence: 99%

“…Salt-like transcription factor 4 (SALL4) is a regulator of embryonic stem cells involved in self-renewal and pluripotency. 5 SALL4 is a novel cancer target, 6 and has been studied in different tumors. For example, SALL4 was increased in breast cancer, and its upregulation was associated with regulating cell growth, invasion and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Salt‐like transcription factor 4 promotes laryngeal cancer progression through transcriptional activation of ubiquitin‐specific protease 21 to stabilize Yin Yang 1

Liu¹,

Gao

et al. 2022

Pathology International

View full text Add to dashboard Cite

Laryngeal cancer (LC) is a rare and challenging clinical problem. Our aim was to investigate the mechanism of salt-like transcription factor 4 (SALL4) in LC. LC tissue and paracancerous tissue were collected. Relative mRNA or protein levels were measured by quantitative real-time polymerase chain reaction or Western blot. MTT, wound healing, and transwell assay were performed to evaluate cell proliferation, migration and invasion. The binding relationship between SALL4 and USP21 promoter was verified by dual-luciferase assay and ChIP. Co-IP and glutathione-S-transferase (GST)-pull down were performed to measure the protein interaction between USP21 and YY1. Additionally, YY1 ubiquitination level was analyzed. It was found that SALL4 mRNA and SALL4 protein levels were elevated in LC clinical tissues and various LC cells. Knockdown of SALL4 inhibited epithelial-mesenchymal transition (EMT) of LC cells. USP21 was transcriptionally activated by SALL4. Co-IP and GST-pull down confirmed USP21 interacted with YY1. USP21 protected YY1 from degradation through deubiquitination. Furthermore, overexpression of USP21 reversed the effect of knockdown of SALL4 on YY1 and EMT in LC cells. In general, SALL4 facilitated EMT of LC cells through modulating USP21/YY1 axis.

show abstract

SALL4 Oncogenic Function in Cancers: Mechanisms and Therapeutic Relevance

Cited by 28 publications

References 211 publications

SALL4: An Intriguing Therapeutic Target in Cancer Treatment

SALL4: An Intriguing Therapeutic Target in Cancer Treatment

Role of SALL4 in HER2+ Breast Cancer Progression: Regulating PI3K/AKT Pathway

Salt‐like transcription factor 4 promotes laryngeal cancer progression through transcriptional activation of ubiquitin‐specific protease 21 to stabilize Yin Yang 1

Contact Info

Product

Resources

About