Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1

Zhang, Jinqiu; Tam, Wai Leong; Tong, Guo Qing; Wu, Qiang; Chan, Hsiao-Yun; Soh, Boon Seng; Lou, Yuefei; Yang, Jianchang; Ma, Yupo; Chai, Li; Ng, Huck‐Hui; Lufkin, Thomas; Robson, Paul; Lim, Bing

doi:10.1038/ncb1481

Cited by 508 publications

(455 citation statements)

References 26 publications

Supporting

Mentioning

440

Contrasting

Unclassified

Order By: Relevance

“…[20][21][22][23] SALL4 forms a regulatory circuit with OCT4, NANOG, and SOX2 to maintain embryonic stem cell pluripotency and self-renewal. [24][25][26][27][28][29] In this self-stabilizing network, SALL4 regulates OCT4 transcription, suggesting acting upstream of OCT4. 28 In this study we have shown that SALL4 has a broader expression pattern than OCT4 in primary germ cell tumors of the CNS.…”

Section: Discussionmentioning

confidence: 96%

“…[24][25][26][27][28][29] In this self-stabilizing network, SALL4 regulates OCT4 transcription, suggesting acting upstream of OCT4. 28 In this study we have shown that SALL4 has a broader expression pattern than OCT4 in primary germ cell tumors of the CNS. OCT4 only labeled germinomas and embryonal carcinomas, whereas SALL4 not only stained germinomas and embryonal carcinomas but also all yolk sac tumors and some teratomas (9/14) and choriocarcinomas (2/3).…”

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Diagnostic utility of SALL4 in primary germ cell tumors of the central nervous system: a study of 77 cases

et al. 2009

View full text Add to dashboard Cite

Primary germ cell tumors of the central nervous system (CNS) sometimes pose diagnostic difficulty. In this study we analyzed the diagnostic utility of a novel marker, SALL4, in 77 such tumors (59 pure and 18 mixed) consisting of the following tumors/tumor components: 49 germinomas, 7 embryonal carcinomas, 27 yolk sac tumors, 3 choriocarcinomas, and 14 teratomas. We also stained SALL4 in 99 primary non-germ cell tumors to test SALL4 specificity. We compared SALL4 with OCT4 in all germ cell tumors and compared SALL4 with a-fetoprotein and glypican-3 in all yolk sac tumors. The staining was semiquantitatively scored as 0 (no staining), 1 þ (o ¼ 30%), 2 þ (31-60%), 3 þ (61-90%), and 4 þ (490%). Strong SALL4 staining was observed in all 49 germinomas (4 þ in 48, 3 þ in 1), 7 embryonal carcinomas (all 4 þ ), and 27 yolk sac tumors (1 þ in 1, 2 þ in 2, 3 þ in 7, 4 þ in 17). SALL4 staining, 1 þ weak to focally strong, was observed in 2 of 3 choriocarcinomas (in mononucleated trophoblasts) and in 9 of 14 teratomas (in primitive neuroepithelium and teratomatous glands). All germinomas and embryonal carcinomas showed strong OCT4 staining (4 þ in all except 1 germinoma with 3 þ ), whereas other germ cell tumors were negative. Out of 27 yolk sac tumors, 26 showed positive a-fetoprotein staining (1 þ in 9, 2 þ in 7, 3 þ in 5, and 4 þ in 5). All yolk sac tumors showed positive glypican-3 staining (1 þ in 6, 2 þ in 6, 3 þ in 7, and 4 þ in 8). The mean percentage of yolk sac tumor cells stained was 84% with SALL4, 45% with a-fetoprotein, and 63% with glypican-3 (Po0.01). No non-germ cell tumors showed SALL4 staining. Our results indicate that SALL4 is a novel sensitive diagnostic marker for primary germ cell tumors of the CNS with high specificity. SALL4 is a more sensitive marker than a-fetoprotein and glypican-3 for yolk sac tumors.

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 96%

Diagnostic utility of SALL4 in primary germ cell tumors of the central nervous system: a study of 77 cases

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Using gene expression profiling approaches, we recently identified the activation of transcription factor Sal-like protein 4transcription factor which plays a fundamental role in the maintenance of embryonic stem cells, possibly through interaction with octamer-binding transcription factor 4, sex determining region Y-box 2, and Nanog [19][20][21][22][23][24]. It has been reported by three independent groups that SALL4 is a biomarker of HCCs with stem-like gene expression signatures and a poor prognosis [18,25,26].…”

Section: Introductionmentioning

confidence: 99%

Defeating EpCAM+ liver cancer stem cells by targeting chromatin remodeling enzyme CHD4 in human hepatocellular carcinoma

Nio

Yamashita

Okada

et al. 2015

Journal of Hepatology

View full text Add to dashboard Cite

Background & Aims: Hepatocellular carcinoma is composed of a subset of cells with enhanced tumorigenicity and chemoresistance that are called cancer stem (or stem-like) cells. We explored the role of chromodomain-helicase-DNA-binding protein 4, which is encoded by the CHD4 gene and is known to epigenetically control gene regulation and DNA damage responses in EpCAM + liver cancer stem cells. Methods: Gene and protein expression profiles were determined by microarray and immunohistochemistry in 245 and 144 hepatocellular carcinoma patients, respectively. The relationship between gene/protein expression and prognosis was examined. The functional role of CHD4 was evaluated in primary hepatocellular carcinoma cells and in cell lines in vitro and in vivo. Results: CHD4 was abundantly expressed in EpCAM + hepatocellular carcinoma with expression of hepatic stem cell markers and poor prognosis in two independent cohorts. In cell lines, CHD4 knockdown increased chemosensitivity and CHD4 overexpression induced epirubicin chemoresistance. To inhibit the functions of CHD4 that are mediated through histone deacetylase and poly (ADP-ribose) polymerase, we evaluated the effect of the histone deacetylase inhibitor suberohydroxamic acid and the poly (ADP-ribose) polymerase inhibitor AG-014699. Treatment with either suberohydroxamic acid or AG-014699 reduced the number of EpCAM + liver cancer stem cells in vitro, and suberohydroxamic acid and AG-014699 in combination successfully inhibited tumor growth in a mouse xenograft model.Conclusions: CHD4 plays a pivotal role in chemoresistance and the maintenance of stemness in liver cancer stem cells and is therefore a good target for the eradication of hepatocellular carcinoma. Ó

show abstract

“…[26][27][28] Recent studies have shown that the maintenance of pluripotency and self-renewal of embryonic stem cells is controlled by a regulatory circuit that includes not only OCT4, NANOG, and SOX2 but also SALL4. 26,29,30 In this network, SALL4 appears to control transcription of OCT4. 29 The relation between SALL4 and OCT4, NANOG, and SOX2 suggests that SALL4 might be also a marker for metastatic germ cell tumors.…”

mentioning

confidence: 99%

“…26,29,30 In this network, SALL4 appears to control transcription of OCT4. 29 The relation between SALL4 and OCT4, NANOG, and SOX2 suggests that SALL4 might be also a marker for metastatic germ cell tumors. The goal of the current study was to investigate the potential utility of SALL4 as a diagnostic marker in a large series of 90 metastatic germ cell tumors from the testis (n ¼ 73), ovary (n ¼ 13), and extragonadal sites (n ¼ 4).…”

mentioning

confidence: 99%

SALL4 is a novel sensitive and specific marker for metastatic germ cell tumors, with particular utility in detection of metastatic yolk sac tumors

Cao¹,

Humphrey²,

Allan³

2009

Cancer

143

115

View full text Add to dashboard Cite

BACKGROUND:The correct diagnosis of metastatic germ cell tumors is critical, because these tumors can be effectively treated and are even cured with modern therapy. Their histopathologic diagnosis can be challenging without immunohistochemical markers, which currently have limitations. SALL4 is a novel stem cell marker essential to maintain pluripotency and self‐renewal of embryonic stem cells. In the current study, the authors investigated the utility of SALL4 as a potential diagnostic marker for metastatic germ cell tumors.METHODS:Ninety metastatic germ cell tumors from testis, ovary, and extragonadal sites were stained with a monoclonal SALL4 antibody. In addition, 170 metastatic nongerm cell malignancies, including 158 carcinomas (6 head and neck, 8 thyroid, 12 lung, 8 breast, 7 hepatocellular, 3 cholangiocarcinomas, 2 ampullary, 10 pancreatic, 18 gastric, 15 esophageal, 10 renal cell, 10 urothelial, 12 prostatic, 18 ovarian, 6 uterine, and 13 colonic) and 12 melanomas, were also stained to test SALL4 specificity.RESULTS:All 22 seminomas, 7 dysgerminomas, 22 embryonal carcinomas, and 14 of 15 yolk sac tumors displayed strong and diffuse SALL positivity in >90% of tumor cells (80% of tumor cells were strongly positive in the remaining yolk sac tumor). Five of 7 choriocarcinomas and 9 of 18 teratomas were also variably positive for SALL4. In contrast, only 10 (esophageal, gastric, and colonic adenocarcinomas) of 170 metastatic somatic tumors demonstrated focally weak SALL4 reactivity (<25% tumor cells).CONCLUSIONS:SALL4 is a novel sensitive and highly specific marker for metastatic germ cell tumors, and is particularly useful for detecting metastatic yolk sac tumors. Cancer 2009. © 2009 American Cancer Society.

show abstract

Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1

Cited by 508 publications

References 26 publications

Diagnostic utility of SALL4 in primary germ cell tumors of the central nervous system: a study of 77 cases

Diagnostic utility of SALL4 in primary germ cell tumors of the central nervous system: a study of 77 cases

Defeating EpCAM+ liver cancer stem cells by targeting chromatin remodeling enzyme CHD4 in human hepatocellular carcinoma

SALL4 is a novel sensitive and specific marker for metastatic germ cell tumors, with particular utility in detection of metastatic yolk sac tumors

Contact Info

Product

Resources

About