Topic
SALL4
About: SALL4 is a research topic. Over the lifetime, 183 publications have been published within this topic receiving 5666 citations. The topic is also known as: DRRS & HSAL4.
Papers published on a yearly basis
Papers
TL;DR: Evidence is presented in 5 of 8 affected families that mutation at this locus results in the Okihiro syndrome phenotype, and the human SALL4 gene on chromosome 20q13-q13.2 is characterized.
Abstract: Okihiro syndrome refers to the association of forearm malformations with Duane syndrome of eye retraction. Based on the reported literature experience, clinical diagnosis of the syndrome can be elusive, owing to the variable presentation in families reported. Specifically, there is overlap of clinical features with other conditions, most notably Holt-Oram syndrome, a condition resulting from mutation of the TBX5 locus and Townes-Brocks syndrome, known to be caused by mutations in the SALL1 gene. Arising from our observation of several malformations in Okihiro syndrome patients which are also described in Townes-Brocks syndrome, we postulated that Okihiro syndrome might result from mutation of another member of the human SALL gene family. We have characterized the human SALL4 gene on chromosome 20q13.13-q13.2. Moreover, we have identified literature reports of forelimb malformations in patients with cytogenetically identifiable abnormalities of this region. We here present evidence in 5 of 8 affected families that mutation at this locus results in the Okihiro syndrome phenotype.
329 citations
TL;DR: It is shown that a targeted null mutation in the mouse Sall4 gene leads to lethality during peri-implantation, and some symptoms of Townes-Brocks syndrome caused by Sall1 truncations could result from SALL4 inhibition.
Abstract: Mutations in SALL4, the human homolog of the Drosophila homeotic gene spalt (sal), cause the autosomal dominant disorder known as Okihiro syndrome. In this study, we show that a targeted null mutation in the mouse Sall4 gene leads to lethality during peri-implantation. Growth of the inner cell mass from the knockout blastocysts was reduced, and Sall4-null embryonic stem (ES) cells proliferated poorly with no aberrant differentiation. Furthermore, we demonstrated that anorectal and heart anomalies in Okihiro syndrome are caused by Sall4 haploinsufficiency and that Sall4/Sall1 heterozygotes exhibited an increased incidence of anorectal and heart anomalies, exencephaly and kidney agenesis. Sall4 and Sall1 formed heterodimers, and a truncated Sall1 caused mislocalization of Sall4 in the heterochromatin; thus, some symptoms of Townes-Brocks syndrome caused by SALL1 truncations could result from SALL4 inhibition.
284 citations
TL;DR: The absence of Sall4 expression in the healthy adult liver enhances the potential of SALL4 as a treatment target in hepatocellular carcinoma, and loss-of-function studies confirmed the critical role of Salls4 in cell survival and tumorigenicity.
Abstract: Background Hepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. In the heterogeneous group of hepatocellular carcinomas, those with characteristics of embryonic stem-cell and progenitor-cell gene expression are associated with the worst prognosis. The oncofetal gene SALL4, a marker of a subtype of hepatocellular carcinoma with progenitor-like features, is associated with a poor prognosis and is a potential target for treatment. Methods We screened specimens obtained from patients with primary hepatocellular carcinoma for the expression of SALL4 and carried out a clinicopathological analysis. Loss-of-function studies were then performed to evaluate the role of SALL4 in hepatocarcinogenesis and its potential as a molecular target for therapy. To assess the therapeutic effects of a peptide that targets SALL4, we used in vitro functional and in vivo xenograft assays. Results SALL4 is an oncofetal protein that is expressed in the human fetal liver and silenced in the adult li...
269 citations
TL;DR: The murine model provides a useful platform to study human MDS/AML transformation, as well as the Wnt/beta-catenin pathway's role in the pathogenesis of leukemia stem cells.
244 citations
TL;DR: SALL4′s expression is an indicator of stem cells, a prognostic marker in liver cancers, correlates with cell and tumor growth, with resistance to 5‐FU, and its suppression results in differentiation and slowed tumor growth.
196 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 17 |
| 2020 | 25 |
| 2019 | 12 |
| 2018 | 15 |
| 2017 | 11 |
| 2016 | 22 |