High cytoplasmic expression of SALL4 predicts a malignant phenotype and poor prognosis of breast invasive ductal carcinoma

Yue, Xiaojing; Xiao, Lei; Yang, Yiling; Liu, W; Zhang, K; Shi, Guang-yi; Zhou, Hongyu; Geng, Jianxiong; Xie, Ning; Wu, Jian‐Yi; Zhang, Q

doi:10.4149/neo_2015_119

Cited by 29 publications

(27 citation statements)

References 35 publications

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“…Interestingly, the ESC markers SOX2, OCT4, SALL4, pSTAT3, and NANOG, showed both nuclear and cytoplasmic expression. This novel finding in MDBMSCC is consistent with previous studies reporting on cytoplasmic expression of NANOG in cervical cancer ( 38 ) and SALL4 in breast cancer ( 39 ) cells, inferring cytoplasmic expression as a predictor of poor prognosis ( 39 ). The reasons for this are the topic of further investigation.…”

Section: Discussionsupporting

confidence: 92%

Characterization of Cancer Stem Cells in Moderately Differentiated Buccal Mucosal Squamous Cell Carcinoma

Featherston

Tan

et al. 2016

Front. Surg.

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AimTo identify and characterize cancer stem cells (CSC) in moderately differentiated buccal mucosa squamous cell carcinoma (MDBMSCC).MethodsFour micrometer-thick, formalin-fixed, paraffin-embedded MDBMSCC samples from six patients underwent 3,3-diaminobenzidine (DAB) immunohistochemical (IHC) staining for the embryonic stem cell (ESC) markers, NANOG, OCT4, SALL4, SOX2, and pSTAT3; cancer stem cell marker, CD44; squamous cell carcinoma (SCC) marker, EMA; and endothelial marker, CD34. The transcriptional activities of the genes encoding NANOG, OCT4, SOX2, SALL4, STAT3, and CD44 were studied using NanoString gene expression analysis and colorimetric in situ hybridization (CISH) for NANOG, OCT4, SOX2, SALL4, and STAT3.ResultsDiaminobenzidine and immunofluorescent (IF) IHC staining demonstrated the presence of (1) an EMA+/CD44+/SOX2+/SALL4+/OCT4+/pSTAT3+/NANOG+ CSC subpopulation within the tumor nests; (2) an EMA−/CD44−/CD34−/SOX2+/OCT4+/pSTAT3+/NANOG+ subpopulation within the stroma between the tumor nests; and (3) an EMA−/CD44−/CD34+/SOX2+/SALL4+/OCT4+/pSTAT3+/NANOG+ subpopulation on the endothelium of the microvessels within the stroma. The expression of CD44, SOX2, SALL4, OCT4, pSTAT3, and NANOG was confirmed by the presence of mRNA transcripts, using NanoString analysis and NANOG, OCT4, SOX2, SALL4, and STAT3 by CISH staining.ConclusionThis study demonstrated a novel finding of three separate CSC subpopulations within MDBMSCC: (1) within the tumor nests expressing EMA, CD44, SOX2, SALL4, OCT4, pSTAT3, and NANOG; (2) within the stroma expressing SOX2, SALL4, OCT4, pSTAT3, and NANOG; and (3) on the endothelium of the microvessels within the stroma expressing CD34, SOX2, SALL4, OCT4, pSTAT3, and NANOG.

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Section: Discussionsupporting

confidence: 92%

Characterization of Cancer Stem Cells in Moderately Differentiated Buccal Mucosal Squamous Cell Carcinoma

Featherston

Tan

et al. 2016

Front. Surg.

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“…Our data showed that inhibition of EGFR pathway resulted in the downregulation of SALL4, and knockdown of SALL4 affected the self-renewal properties of CSCs. The enrichment of cells with CSCs markers (CD44 high /CD24 low ) and phenotypes in Erlotinib resistant NSCLC cell lines has been reported 32 , 35 . These observations suggest that CSCs was also selected during prolonged exposure to EGFR TKIs and contribute significantly to drug resistance and tumor relapse.…”

Section: Discussionmentioning

confidence: 98%

Upregulation of SALL4 by EGFR activation regulates the stemness of CD44-positive lung cancer

Liu

et al. 2018

Oncogenesis

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The transcriptional factor SALL4, an important stem cell regulator, is expressed in hematopoietic stem cells and various malignancies, but its role in EGFR-mutated NSCLCs has not been studied yet. Here, we report that the expression of Sal-like protein 4 (SALL4), was significantly higher in EGFR mutated lung tumors than in non-tumor tissue. SALL4-high lung cancer patients had poorer prognosis after surgery than SALL4-low patients. The expression of SALL4 could be induced by the activation of EGFR through the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. The knockdown of SALL4 expression could suppress spheroid formation and the expression of lung cancer stem cell marker CD44. More interestingly, the knockdown of SALL4 expression could suppress the migration, invasion, and metastasis of the lung cancer cells and significantly increase the sensitivity of EGFR mutated cells to Erlotinib. These results suggest that SALL4 may be a novel potential therapeutic target for the diagnosis and treatment of lung cancer.

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“…Analyses of its expression and epigenetic status have shown that SALL4 is de-regulated and aberrantly expressed in various cancers (Review in 64 ) such as leukemia 65 , germ cell tumors 6667 , hepatocellular carcinoma (HCC) 2468 , gastric cancer 20,69–73 , colorectal carcinoma 74–76 , esophageal squamous cell carcinoma 77,78 , breast cancer 79–81 , endometrial cancer 82,83 , lung cancer 84–86 and glioma 87 . Functionally, SALL4 is important for the survival 38,80,82,88–93 , drug resistance 82,94 and metastasis 69,82 of many of these cancer cells (Figure 4).…”

Section: Sall4 In Cancersmentioning

confidence: 99%

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

Tatetsu

Kong

Gao

et al. 2016

Gene

109

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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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High cytoplasmic expression of SALL4 predicts a malignant phenotype and poor prognosis of breast invasive ductal carcinoma

Cited by 29 publications

References 35 publications

Characterization of Cancer Stem Cells in Moderately Differentiated Buccal Mucosal Squamous Cell Carcinoma

Characterization of Cancer Stem Cells in Moderately Differentiated Buccal Mucosal Squamous Cell Carcinoma

Upregulation of SALL4 by EGFR activation regulates the stemness of CD44-positive lung cancer

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

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