Overexpression of SALL4 in lung cancer and its importance in cell proliferation

Kobayashi, Daisuke; Kuribayashi, Kageaki; Tanaka, Maki; Watanabe, Naoki

doi:10.3892/or.2011.1374

Cited by 50 publications

(49 citation statements)

References 24 publications

(32 reference statements)

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“…(28, 29) As a marker for stem cells, SALL4 expression is proposed to represent a stem cell phenotype in HCC, as shown in other cancer types. (31–35) These studies indicate that stem cell features, defined by nuclear SALL4 immunohistochemistry and/or mRNA expression, correlate with an aggressive course and poor prognosis. Importantly, in both HCC studies, SALL4 immunoreactivity was seen in 55.6% (n=171) and 85% (n=20) of cases, respectively, and overexpression by microarray analysis was detected in 50% of cases.…”

Section: Discussionmentioning

confidence: 95%

SALL4 Immunoreactivity Predicts Prognosis in Western Hepatocellular Carcinoma Patients but Is a Rare Event

Liu

Vachharajani

Chapman

et al. 2014

American Journal of Surgical Pathology

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Prognostic biomarkers that stratify patients with cancer are needed. Recent studies from Asia have implicated SALL4, a stem cell marker, as useful in identifying aggressive cases of hepatocellular carcinoma (HCC), and over 50% of the cases tested had upregulation by microarray or dense immunoreactivity. Given the differences in predominant etiologic factors between the Asian and Western HCC, we sought to determine the prevalence of SALL4 immunoreactivity and its clinical relevance in Western HCC patients. We constructed tissue microarrays from 236 adult HCC. Two cores each of tumor and nontumor tissue were included for each case. SALL4 immunohistochemistry was scored in a semi-quantitative manner and the results correlated with recurrence-free and overall survival, in addition to standard demographics. Among the 236 cases, 165 (70.0%) were male. The median age was 59 years (range: 19–83 years). The majority (78.4%) of patients were Caucasian, followed by African American (15.7%), Asian (3.8%), Hispanic (1.7%), and Native American (0.4%). The majority of patients had hepatitis C (42.8%), followed by alcoholic liver disease and hepatitis B (both 8.9%), and nonalcoholic steatohepatitis (3.8%). SALL4 immunoreactivity was detected in a total of 3 cases (1.3%), and nonreactivity was validated on tissue sections from 73 cases. By univariate analysis, the SALL4-positive cases had significantly higher tumor grade (P = 0.0251), more frequent lymphovascular invasion (P = 0.0150), shorter recurrence-free survival (7.90 vs. 57.54 months; P = 0.0115) and overall survival (7.90 vs. 64.87 months; P = 0.0018). While SALL4 immunoreactivity in Western HCC is correlated with higher grade and poor prognosis, this is a rare event. Therefore, universal application of SALL4 as a biomarker for HCC should be performed with caution.

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Section: Discussionmentioning

confidence: 95%

SALL4 Immunoreactivity Predicts Prognosis in Western Hepatocellular Carcinoma Patients but Is a Rare Event

Liu

Vachharajani

Chapman

et al. 2014

American Journal of Surgical Pathology

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“…In addition, SALL4 promoted the proliferation, invasion, migration, EMT, chemoresistance, and the maintenance of cancer stem cells in different cancer types, and targeted inhibition of SALL4 has shown efficient therapeutic effects on cancer [22, 28, 38–40]. For instance, knockdown of SALL4 causes inhibition of lung cancer cell proliferation, induced by cell cycle arrest at the G1/early S phase [41]. In the present study, we found that restoration of SALL4 reversed the suppressive effect of miR-98 on the proliferation, migration, invasion and EMT of HCC cells, suggesting that miR-98 plays a suppressive role in HCC via inhibition of SALL4.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-98 acts as a tumor suppressor in hepatocellular carcinoma via targeting SALL4

et al. 2016

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MicroRNAs (miRs) are involved in the development and progression of hepatocellular carcinoma (HCC), but the regulatory mechanism of miR-98 in HCC still remains unclear. Here we found that miR-98 was significantly downregulated in HCC tissues compared to matched adjacent normal tissues (ANTs). Low miR-98 expression was associated with tumor size, metastasis, portal vein tumor embolus, and poor overall survival. Ectopic expression of miR-98 decreased the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells. SALL4 was identified as a novel target of miR-98, and the protein expression of SALL4 was inhibited by miR-98 in HCC cells. Overexpression of SALL4 reversed the suppressive effects of miR-98 on the malignant phenotypes of HCC cells. Besides, SALL4, upregulated in HCC tissues compared to the matched ANTs, was inversely correlated to the miR-98 levels in HCC tissues. In addition, overexpression of miR-98 markedly suppressed the tumor growth as well as tumor-induced death in nude mice. In summary, miR-98 plays a suppressive role in the proliferation, migration, invasion and EMT of HCC cells, partly at least, via directly inhibition of SALL4. Therefore, the miR-98/SALL4 axis may become a promising therapeutic target for HCC.

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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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Overexpression of SALL4 in lung cancer and its importance in cell proliferation

Cited by 50 publications

References 24 publications

SALL4 Immunoreactivity Predicts Prognosis in Western Hepatocellular Carcinoma Patients but Is a Rare Event

SALL4 Immunoreactivity Predicts Prognosis in Western Hepatocellular Carcinoma Patients but Is a Rare Event

MicroRNA-98 acts as a tumor suppressor in hepatocellular carcinoma via targeting SALL4

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

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