Sal-like Protein Research Articles

Unraveling the mystery of thalidomide

Developmental Biology Off-label use of thalidomide became a worldwide trend in the 1950s and early 1960s to alleviate morning sickness. It resulted in a historical tragedy, as thousands of babies were born with severe birth defects. Donovan et al. may have found a missing link to explain how the drug affects fetal development. The researchers show that thalidomide and closely related drugs rapidly degrade the transcription factor Sal-like protein 4 (SALL4), which is necessary for fetal limb and organ formation. Adding further weight to their findings, certain individuals with mutations in the SALL4 gene develop abnormalities that resemble thalidomide-induced birth defects. eLife 7 , e38430 (2018).

Landscape of immune microenvironment in hepatocellular carcinoma and its additional impact on histological and molecular classification.

The immune microenvironment of HCC can be classified into three immunosubtypes (Immune-high, Immune-mid, and Immune-low) with additional prognostic impact on histological and molecular classification of HCC. (Hepatology 2018).

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

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.

Research progress of SALL4 gene in human malignant tumor

At present, malignant tumor is a serious threat to human health. Its pathogenesis is complicated and caused by the interaction of various carcinogenic factors in human body. Human sal-like protein 4 (SALL4) is a newly discovered gene. It can play an important role in the function of embryonic stem cells since it is with protein transcription factor of C2H2 zinc fingers. Studies have found that mutations of the gene often lead to the occurrence of malignant tumors. This article reviews the molecular mechanism of SALL4 in the occurrence and development of malignant tumors and its role in the diagnosis and treatment of malignant tumors.

Aberrantly Expressed SALL4 Promotes Cell Proliferation via β-Catenin/c-Myc Pathway in Human Choriocarcinoma Cells.

Sal-like protein 4 (SALL4) has been proved to play a pivotal role in the development and progression of various cancers. Previous studies showed that SALL4 was highly expressed in human choriocarcinoma tissues. However, the role of SALL4 in the biological behavior of human choriocarcinoma cells remains largely unknown. In this study, we first elucidated that SALL4 was highly expressed in human choriocarcinoma cell line JEG-3 and JAR. Sal-like protein 4 knockdown by small interfering RNA (siRNA) decreased c-Myc expression, whereas SALL4 overexpression by transfection of human pLenti-SALL4 construct promoted c-Myc expression. Further data showed that SALL4 overexpression improved cell proliferation of JEG-3 cells, which can be abrogated by c-Myc siRNA. Moreover, our data showed that SALL4 interact with β-catenin and SALL4 overexpression promoted the localization of β-catenin in the nucleus and β-catenin siRNA abrogated SALL4-induced c-Myc expression in JEG-3 cells. These data indicate that aberrantly expressed SALL4 in human choriocarcinoma cells may promote cell proliferation via β-catenin/c-Myc pathway, indicating that SALL4 may be potential treatment targets of human choriocarcinoma.

Expression profiles of stemness genes in gastrointestinal stromal tumor

Gastrointestinal stromal tumor (GIST) is believed to originate from intestinal cells of Cajal or their stem cell precursors, and expresses stemness-related markers, such as CD117, CD34, DOG1 and nestin. To further characterize phenotypic features of GISTs, we examined expression profiles of a panel of stemness genes in GISTs, by analyzing existing gene expression profiling datasets. Our results showed that mRNA levels of B-lymphoma moloney murine leukaemia virus insertion region-1 (BMI1), kruppel-like factor 4 (KLF4), sal-like protein 4 (SALL4) and telomerase reverse transcriptase (TERT) were significantly unregulated in GISTs. Subsequently, protein expression of BMI1 and TERT was identified in GIST specimens by immunohistochemistry. Especially, we found that high expression of nuclear BMI1 was associated with large tumor size (P = .0239), high mitotic count (P < .01), high Ki-67 index (P = .0357), advanced National Institute of Health (NIH) criteria (P = .0025) and advanced World Health Organization (WHO) classification (P < .01) in GISTs. Functional and pathway enrichment analysis showed that most of BMI1's coexpressed genes were involved in tumor growth-related process, such as regulation of cell cycle and proliferation. Furthermore, we confirmed RAS oncogene family (RAB18) and limb development membrane protein 1 (LMBR1) genes as novel targets for BMI1 in GIST cells. These results provide valuable information for the expression profiles of stemness genes in GISTs, and identified nuclear BMI1 as an important marker of GIST cell proliferation and progression.

Methylation-induced downregulation and tumor-suppressive role of microRNA-98 in glioma through targeting Sal-like protein 4.

MicroRNAs (miRs) have been found to play key roles in various human cancers, but the detailed regulatory mechanism of miR-98 in glioma remains largely unknown. The findings of the present study demonstrated that miR-98 was frequently downregulated in glioma tissues and cell lines (U87, U251, U373 and SHG44), and the decreased miR-98 levels were associated with DNA methylation. Treatment with 5-Aza-20-deoxycytidine, a DNA methyltransferase inhibitor, significantly increased the expression of miR-98 in glioma cells. Moreover, both miR-98 downregulation and methylation were significantly associated with a more aggressive tumor phenotype in glioma, as well as shorter survival time of glioma patients. Restoration of miR-98 expression caused a marked decrease in the migration and invasion of U87 cells, but did not affect cell proliferation. Sal-like protein 4 (SALL4) was further identified as a novel target gene of miR-98, and its protein expression was negatively regulated by miR-98 in U87 cells. Restoration of SALL4 expression reversed the suppressive effects of miR-98 on the migration and invasion of U87 cells. Furthermore, SALL4 was significantly upregulated in glioma tissues and cell lines, and an inverse correlation between miR-98 and SALL4 expression in glioma tissues was identified. In addition, the increased expression of SALL4 was significantly associated with glioma progression. Taken together, these data demonstrated that downregulation of miR-98, induced by methylation, promotes glioma cell migration and invasion via targeting SALL4. Therefore, miR-98 may become a potential therapeutic candidate for glioma.

HER2 is frequently overexpressed in hepatoid adenocarcinoma and gastric carcinoma with enteroblastic differentiation: a comparison of 35 cases to 334 gastric carcinomas of other histological types

Aimsα-Fetoprotein (AFP)-producing gastric carcinoma (AFPGC) is one of the most aggressive GC subtypes. Frequent expression of human epidermal growth factor receptor 2 (HER2) has previously been reported in hepatoid adenocarcinoma...

The Prognostic Value of Cytokeratin and Sal-Like Protein 4 Expression in Hepatocellular Carcinoma and Intra-Hepatic Cholangiocarcinoma in Taiwan.

Background: We previously reported that modulation of cytokeratin18 induces pleomorphism of liver cells, higher cell motility, and higher drug sensitivity to sorafenib treatment of hepatoma cells. These relationships were established by in vitro experiments. The aim of this study was to determine the in vivo association between cytokeratin expression and tumor behavior, as well as cancer stem cells of hepatocellular carcinoma and intra-hepatic cholangiocarcinoma in Taiwan.Methods: Cytokeratins and sal-like protein 4 expression was determined in 83 hepatocellular carcinoma and 30 intra-hepatic cholangiocarcinoma specimens by immunohistochemistry. The relationship between cytokeratins and sal-like protein 4 expression with hepatitis virus infection, clinicopathologic factors, and survival was analyzed. Further, the correlation among cytokeratins and sal-like protein 4 expression was studied.Results: In addition to cytokeratin8/18, the expression of cytokeratin7/19 and sal-like protein 4 was noted in hepatocellular carcinoma; however, only cytokeratin19 expression had a significant correlation with poor overall survival and poor disease-free survival. The expression of cytokeratins and sal-like protein 4 was not correlated with hepatitis virus infection. The expression of cytokeratin19, but not 7, 8, and 18, was correlated with sal-like protein 4 expression in hepatocellular carcinoma. Cytokeratin7 expression was decreased and the sal-like protein 4 expression was absent in all 30 intra-hepatic cholangiocarcinoma cases. The expression of cytokeratins had not statistically significant correlation with overall and disease-free survival in patients with intra-hepatic cholangiocarcinoma.Conclusions: The expression of cytokeratin19 was associated with sal-like protein 4 expression, as well as poor overall and disease-free survival in hepatocellular carcinoma patients in Taiwan.

Epigenetic modification of SALL1 as a novel biomarker for the prognosis of early stage head and neck cancer.

This study examined Sal-like protein (SALL)1 methylation profiles in head and neck squamous-cell carcinoma (HNSCC) patients at diagnosis and follow-up, and evaluated their prognostic significance and value as a biomarker. SALL1 expression was examined in a panel of cell lines by quantitative reverse transcription PCR (qRT-PCR). Promoter methylation was determined by quantitative methylation-specific polymerase chain reaction (qMSP) and was compared to the clinical characteristics of 205 samples. SALL1 promoter methylation was associated with transcriptional inhibition and was correlated with disease recurrence in 31.7% of cases, with an odds ratio of 1.694 (95% confidence interval: 1.093-2.626; P = 0.018) by multivariate Cox proportional hazard regression analysis. SALL1 promoter hypermethylation showed highly discriminatory receiver operator characteristic curve profiles that clearly distinguished HNSCC from adjacent normal mucosal tissue, and was correlated with reduced disease-free survival in early stage T1 and T2 patients (log-rank test, P < 0.001). SALL1 methylation was significantly correlated with the methylation status of both SALL3 and CDH1. This study suggests that CpG hypermethylation is a likely mechanism of SALL1 gene inactivation, supporting the hypothesis that SALL1 might play a role in HNSCC tumorigenesis and could serve as an important biomarker.

MicroRNA-219 exerts a tumor suppressive role in glioma via targeting Sal-like protein 4.

MicroRNAs (miRs) serve important roles in the development and progression of various human cancer types, including glioma. Recently, miR-219 has been suggested to function as a tumor suppressor in glioma; however, the underlying mechanism remains largely unknown. The aim of this study was to investigate the regulatory mechanism of miR-219 in the malignant phenotypes of glioma cells. Quantitative polymerase chain reaction (qPCR) and western blotting were conducted to examine the mRNA and protein expression. An MTT assay, wound healing assay and Transwell assay were used to study cell proliferation, migration and invasion. The qPCR data indicated that the expression of miR-219 was significantly decreased in glioma tissues compared with normal brain tissues. In addition, a low expression of miR-219 was identified to be associated with an advanced pathological grade. In vitro experiments demonstrated that miR-219 was also downregulated in several common glioma cell lines, including A172, U87, U251 and U373, when compared with that in normal astrocytes. Ectopic expression of miR-219 caused a significant decrease in U87 cell proliferation, migration and invasion. Luciferase reporter assay data indicated that Sal-like protein 4 (SALL4) was a direct target gene of miR-219, while the protein expression of SALL4 was negatively regulated by miR-219 in U87 cells. Furthermore, SALL4 was significantly upregulated in glioma tissues and cell lines, and upregulation of SALL4 was associated with a higher pathological grade. Furthermore, overexpression of SALL4 significantly attenuated the suppressive effects of miR-219 on U87 cell proliferation, migration and invasion, suggesting that miR-219 serves a suppressive role in glioma growth and metastasis via targeting SALL4. Therefore, the present study highlighted the clinical significance of the miR-219/SALL4 axis in glioma.

Fetal gut–like differentiation in gallbladder cancer

Adenocarcinomas showing fetal gut-like (enteroblastic) differentiation can arise in a variety of organs and are frequently accompanied by an elevated serum α-fetoprotein (AFP) level. However, no study has investigated fetal gut-like differentiation in gallbladder cancer in detail. Herein, we performed morphological and immunohistochemical analyses of fetal gut-like differentiation in 49 consecutive gallbladder cancer cases. The expression of Sal-like protein 4 (SALL4), an embryonic stem cell marker reported to represent fetal gut-like differentiation, as well as other oncofetal proteins, including glypican-3 (GPC3) and AFP, was assessed. We found 1 case of fetal gut-like adenocarcinoma that coexisted with conventional-type adenocarcinoma. The fetal gut-like adenocarcinoma component revealed diffuse immunoreactivity for SALL4 and partial positivity for AFP, whereas the conventional-type adenocarcinoma component was negative. We also found 2 poorly differentiated adenocarcinomas with hepatoid morphology and 1 clear cell carcinoma, none of which showed SALL4 positivity. In other conventional-type adenocarcinomas, focal immunoreactivity for SALL4 and GPC3 was occasionally observed. The overall positivity rates for SALL4 and GPC3 were 12.2% (6/49) and 16.3% (8/49), respectively. SALL4 and GPC3 expression was not associated with clinicopathological factors, including T category, lymphovascular invasion, and lymph node metastases. In conclusion, fetal gut-like adenocarcinoma was found in 2% of our gallbladder cancer series. We conclude that fetal gut-like adenocarcinoma is a distinct histological subtype of gallbladder cancer, characterized by SALL4 expression.

Analysis of putative biomarkers of undifferentiated spermatogonia in dog testis

Spermatogenesis begins after puberty and continues throughout a male’s life, and is regulated by spermatogonial stem cells in the seminiferous tubules. Markers of male germ cells, including undifferentiated spermatogonia to fully developed spermatozoa have been identified in rodents, but not in dogs. In this study, to characterize the markers of undifferentiated spermatogonia, histological and immunohistochemical analyses were performed on pre-pubertal (1-month-old), early pubertal (4-month-old), and post-pubertal (7-month-old) dog testes. Expression of chemokine receptor 4 (CXCR4), insulin-like growth factor binding protein 3 (IGFBP3), LIN28, and Sal-like protein 4 (SALL4) genes was confirmed by immunohistochemical analysis. In pre-pubertal and early pubertal dog testes, CXCR4, IGFBP4, and LIN28 genes were expressed in undifferentiated spermatogonia, whereas the SALL4 gene was not expressed in the pre-pubertal stage. In adult dog testes, CXCR4 and IGFBP3 gene expression was detected in undifferentiated spermatogonia and co-localized with protein gene product 9.5 (PGP9.5) near the basement membrane of the seminiferous tubules. The LIN28 and SALL4 genes were expressed in synaptonemal complex protein 3-positive spermatocytes. The CXCR4 and IGFBP3 gene expression is conserved among other species, while LIN28 and SALL4 gene expression varies. Based on results of the present study, it is suggested that undifferentiated spermatogonia markers detected in other species are conserved in dogs. These results may facilitate further studies of the cellular mechanisms of spermatogenesis in dogs.

A New Indole Derivative Decreased SALL4 Gene Expression in Acute Promyelocytic Leukemia Cell Line (NB4)

Background:Acute myeloblastic leukemia (AML) is a clonal disorder due to bone marrow failure and uncontrolled proliferation of myeloid lineage. Acute promyelocytic leukemia (APL) is a subtype of AML. Heterocyclic compounds, such as indole, are considered as attractive candidates for cancer therapy, due to their abundance in nature and known biological activity. Sal-like protein (SALL4) is a zinc finger transcription factor involving in the multi-potency of stem cells, in the NB4 cell line. This study was aimed to evaluate the effects of basal indole and its new derivative, 2-(1-((2, 4-Aril)imino)-2,2,2-trifluoroethyl) phenyl-1H Indole-3- carbaldehyde (TFPHC), on the expression of SALL4.Methods:Cells were cultured and treated with different concentrations (75, 150, and 300 µg/mL) of the new indole derivative and DMSO, as a vehicle control, for 24 and 48 hours. Cell proliferation was evaluated by using Trypan blue exclusion and MTT assays. The percentage of apoptotic cells was determined by flowcytometry analysis using the Annexin V/PI apoptosis detection kit; mRNA expression of SALL4 was studied using absolute quantitative RT-PCR.Results:Our findings demonstrated the effects of new indole derivatives on SALL4 mRNA expression. Expression of SALL4 mRNA was significantly decreased at 75, 150, and 300 µg/mL concentrations.Conclusion:SALL4 plays a role in the survival of APL cells. SALL4 expression could be suppressed by the novel indole derivative. Additionally, SALL4 gene suppression can serve as a target in APL therapy.

MicroRNA-181b Inhibits Cellular Proliferation and Invasion of Glioma Cells via Targeting Sal-Like Protein 4.

MicroRNAs (miRs), a class of noncoding RNAs that are 18–25 nucleotides in length, are able to suppress gene expression by targeting complementary regions of mRNAs and inhibiting protein translation. Recently, miR-181b was found to play a suppressive role in glioma, but the regulatory mechanism of miR-181b in the malignant phenotypes of glioma cells remains largely unclear. In this study, we found that miR-181b was significantly downregulated in glioma tissues when compared with normal brain tissues, and decreased miR-181b levels were significantly associated with high-grade pathology and a poor prognosis for patients with glioma. Moreover, miR-181b was downregulated in glioma cell lines (U87, SHG44, U373, and U251) compared to normal astrocytes. Overexpression of miR-181b significantly decreased the proliferation, migration, and invasion of glioma U251 cells. Sal-like protein 4 (SALL4) was identified as a novel target gene of miR-181b in U251 cells. The expression of SALL4 was significantly upregulated in glioma tissues and cell lines, and an inverse correlation was observed between the miR-181b and SALL4 expression levels in glioma. Further investigation showed that the protein expression of SALL4 was negatively regulated by miR-181b in U251 cells. Knockdown of SALL4 significantly inhibited the proliferation, migration, and invasion of U251 cells, while overexpression of SALL4 effectively reversed the suppressive effects of miR-181b on these malignant phenotypes of U251 cells. In conclusion, our study demonstrates that miR-181b has a suppressive effect on the malignant phenotypes of glioma cells, at least partly, by directly targeting SALL4. Therefore, the miR-181b/SALL4 axis may become a potential therapeutic target for glioma.

Higher expression of SALL4 predicts poor cancer prognosis: A meta-analysis.

Sal-like protein 4 (SALL4) is recognized as a potential biomarker for assessing cancer prognosis. Many experiments have been done to explore the aberrant expression of SALL4 in cancer patients. To explore the association between SALL4 expression and cancer prognosis. A systematically comprehensive search was performed through PubMed, Web of Science, and CNKI. The prognostic value of SALL4 expression in cancer patients was evaluated by pooled hazard ratios (HRs) and 95% confidence intervals (CIs). The overexpression of SALL4 was identified to be significantly associated with a poor prognosis in cancer patients (pooled HR: 2.02, 95% CI: 1.67-2.46). This association was also detected in digestive system neoplasms subgroup (pooled HR: 1.91, 95% CI: 1.52-2.39) and reproductive system neoplasms subgroup (pooled HR: 1.95, 95% CI: 1.17-3.26). In the geography subgroup analysis, a statistical association was confirmed in the Chinese subgroup (pooled HR: 1.982, 95% CI: 1.526-2.576). In the respect of disease progression, there was a certain degree of relationship between higher expression of SALL4 and recurrence-free survival (RFS) (pooled HR: 1.617, 95% CI: 1.190-2.196). SALL4 is a promising prognostic biomarker for cancer, and is appropriate for the assessment of cancer prognosis in the Chinese people.

Stage-specific expression of Sal-like protein 4 in boar testicular germ cells

Spermatogenesis, the complex process of sperm cell development including mitotic cell division and meiosis, relies on spermatogonial stem cells (SSCs). While markers for developing germ cells have been well investigated in mice, developmental stage-specific markers of germ cells in domestic animals have not been identified. Sal-like protein 4 (SALL4) is known as a putative marker for undifferentiated spermatogonia in rodents; however, its expression in domestic animals has not been investigated. The objective of this study was to characterize the expression of SALL4 in the developmental stages of boar testes and SSCs. Interestingly, all SALL4-expressing cells responded positively to PGP9.5, which is known as a spermatogonia marker in boar testes, while some PGP9.5-positive cells did not express SALL4 in pre-pubertal boar testes. At this stage, the expression of SALL4 was observed in GFRα1-positive cells, and its expression was maintained in cultured pSSCs in vitro, suggesting that SALL4 is a marker of early-stage boar spermatogonia that express GFRα1 in pre-pubertal testes. Additionally, SALL4 expression was observed in c-Kit-positive but not in PGP9.5- or SCP3-positive cells in post-pubertal testes. In conclusion, SALL4 is expressed in early undifferentiated spermatogonia in pre-pubertal boar testes and in primary spermatocytes in post-pubertal boar testes. Therefore, SALL4 can be used as a stage-specific marker of developing germ cells in boar testes.

Epigenetic silencing of SALL3 is an independent predictor of poor survival in head and neck cancer

BackgroundThis study examined Sal-like protein (SALL)3 methylation profiles of head and neck cancer (HNSCC) patients at diagnosis and follow-up and evaluated their prognostic significance and value as a biomarker. SALL3 expression was examined in a panel of cell lines by quantitative reverse transcription polymerase chain reaction (RT-PCR). The methylation status of the SALL3 promoter was examined by quantitative methylation-specific PCR.ResultsSALL3 promoter methylation was associated with transcriptional inhibition and was correlated with disease recurrence in 64.8% of cases, with an odds ratio of 1.914 (95% confidence interval: 1.157–3.164; P = 0.011) by multivariate Cox proportional hazard regression analysis. SALL3 promoter hypermethylation showed highly discriminatory receiver operator characteristic curve profiles that clearly distinguished HNSCC from adjacent normal mucosal tissue, and was correlated with reduced disease-free survival (DFS) (log-rank test, P = 0.01). Hypermethylation of tumor-related genes was higher among patients with SALL3 methylation than among those without methylation (P < 0.001). Furthermore, SALL3 hypermethylation was associated with expression of TET1, TET2, and DNMT3A genes.ConclusionsThis study suggests that CpG hypermethylation is a likely mechanism of SALL3 gene inactivation, supporting the hypothesis that the SALL3 gene may play a role in the tumorigenesis of HNSCC and may serve as an important biomarker.

Gastric hepatoid adenocarcinoma resulting in a spontaneous gastric perforation: a case report and review of the literature

BackgroundGastric hepatoid adenocarcinoma (GHAC) is an atypical form of gastric cancer (GC) that has similar tissue morphology to hepatocellular carcinoma and frequently produces alpha-fetoprotein. We present an exceedingly rare case of GHAC resulting in a spontaneous gastric perforation.Case presentationA 61-year-old man presented at our institution complaining of abdominal and back pain. A computed tomography scan revealed a spontaneous gastric perforation with a solitary liver tumor and lymph node swelling. Following a diagnosis of advanced-stage GC with a gastric perforation, perforative peritonitis, multiple lymph node metastases, and a solitary metastasis of the lateral segment of the liver, the patient underwent distal gastrectomy. Histopathology of the resected specimen revealed that the tumor cells were arranged in a hepatoid pattern. On immunohistochemical staining, the tumor cells were positive for alpha-fetoprotein and Sal-like protein 4. Thus, the patient was diagnosed with GHAC. Hepatic resection of the solitary liver metastasis was performed. However, recurrence occurred and the patient achieved complete response following tegafur/gimeracil/oteracil-based chemotherapy.ConclusionsGHAC is a highly malignant histological subtype of GC. We reported on an extremely rare case of GHAC resulting in a spontaneous gastric perforation and reviewed the literature, including epidemiological data, treatment regimens, and the association between GHAC and alpha-fetoprotein-producing GC.

Knockdown of SALL4 Inhibits Proliferation, Migration, and Invasion in Osteosarcoma Cells.

Sal-like protein 4 (SALL4) is a zinc finger transcription factor that has been reported to be aberrantly expressed in several human malignancies and identified as an oncogene. However, the potential role of SALL4 in osteosarcoma remains to be elucidated. In this study, we explored the biological functions of SALL4 in osteosarcoma. We found that SALL4 was overexpressed in osteosarcoma tissues and cell lines. Knockdown of SALL4 inhibited osteosarcoma cell proliferation, migration, and invasion in vitro. In addition, SALL4 knockdown suppressed osteosarcoma growth and metastasis in vivo. We also showed that SALL4 knockdown decreased the protein expression of Wnt3a and β-catenin in osteosarcoma cells. Taken together, our study showed that SALL4 plays an important role in regulating the proliferation, migration, and invasion of osteosarcoma cells. Thus, SALL4 may represent a potential therapeutic target in the treatment of osteosarcoma.