Redundant roles of Sox17 and Sox18 in early cardiovascular development of mouse embryos

Sakamoto, Youhei; Hara, Kenshiro; Kanai‐Azuma, Masami; Matsui, Toshiyasu; Miura, Yutaroh; Tsunekawa, Naoki; Kurohmaru, Masamichi; Saijoh, Yukio; Koopman, Peter; Kanai, Yoshikatsu

doi:10.1016/j.bbrc.2007.06.093

Cited by 162 publications

(168 citation statements)

References 27 publications

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“…[19][20][21][22][23][24][25][26][27][28][29][30] In fact, few studies have revealed the significance of SOX group F gene expression in human cancer, although cell line-based studies have demonstrated that both SOX 18 and SOX 7 were highly expressed in several strains of gastric, pancreatic and esophageal cancer cell lines. 22,32 In the present study, SOX group F gene expression determined by RT-PCT was increased in gastric cancer tissues than in normal gastric tissues obtained from the same individuals.…”

Section: Discussionmentioning

confidence: 99%

“…17 SOX 18 is transiently expressed in the endothelial cells of all developing blood vessels and has a key role in both vascular development and postnatal neovascularization. 15,[19][20][21] SOX 18 is highly expressed in the ventricles and interventricular septum of the normal adult heart, and relatively highly expressed in the gastrointestinal tract, i.e., in the stomach and jejunum. 22 SOX 18 expression is also reactivated during adult neovascularization associated with wound healing and tumorigenesis.…”

mentioning

confidence: 99%

“…[25][26][27][28] The SOX 7 and SOX 17 genes are also known to have compensatory roles during angiogenesis and lymphangiogenesis. [19][20][21] It has been demonstrated that blood circulation in SOX 7 and SOX 18 double knock-down zebrafish was blocked in the trunk and tail due to multiple fusions between the axial vessels. 19 Furthermore, SOX 17/SOX 18-double null mouse embryos also developed severe abnormal defects during the formation of the anterior dorsal aorta and of the cervical microvasculature.…”

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confidence: 99%

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The lymphangiogenic factor SOX 18: A key indicator to stage gastric tumor progression

Eom¹,

Jo²,

Kook³

et al. 2011

Intl Journal of Cancer

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SOX group F genes are important regulators of angiogenesis and lymphangiogenesis. The aim of the present study was to examine the relationships between Sox group F expression and clinicopathological factors in gastric cancer. Three hundred and fifteen gastric cancer tissues and the corresponding normal gastric tissue were obtained from the tumor bank at the National Cancer Center, Korea. SOX group F mRNA levels in these tissues were evaluated by reverse transcriptase polymerase chain reaction (RT-PCR). The serum levels of SOX 18 proteins in 219 gastric cancer patients and in 30 healthy volunteers were also measured by enzyme-linked immunosorbent assay. Furthermore, immunohistochemistry (IHC) was performed on 679 gastric cancer tissues and the clinicopathological characteristics, as well as the survival rates of SOX 18 positive and negative gastric cancers were compared. RT-PCR showed that SOX group F mRNA was increased in the gastric cancer tissues compared to the normal gastric tissues (p < 0.001, respectively). The serum levels of SOX 18 protein were also increased in gastric cancer patients compared to healthy volunteers. IHC showed that of the 679 gastric cancer cases, 177 (26.1%) were positive for SOX 18 expression in their tumor stroma, and the frequencies of both lymphovascular invasion and lymph node metastases were higher in the SOX 18 positive than in the negative group. Both the 5-year survival and the recurrence-free survival were shorter for SOX 18 positive tumors (p 5 0.023 and 0.012, respectively). SOX 18 expression might be a prognostic tumor marker and a potential therapeutic target in gastric cancer.Gastric cancer is the fourth most common cancer in the world and, annually, about 1 million new cases are diagnosed worldwide. 1 In South Korea, gastric cancer has a higher incidence than any other cancer, and is the third most common cause of death from cancer. 2 The prognosis of patients with gastric cancer is influenced by the presence of lymph node (LN) metastasis, therefore, an accurate and reliable indicator is required to predict the presence of LN metastasis. Furthermore, a biomolecular predictor of LN metastasis can be a prognostic marker or a potential therapeutic target. [3][4][5] Recently, angiogenesis and lymphangiogenesis were found to be critically required for solid tumor growth, invasion and distant metastases. 6-8 Previous molecular and cellular analyses have identified a number of factors of angiogenesis and lymphangiogenesis, such as, the fibroblast growth factor, the vascular endothelial growth factor and angiopoietin. 9-13 Similarly, specific gene-based studies recently discovered the lymphangiogenesis associated SOX genes (i.e., sex determining region Y box genes). 14,15 The SOX genes constitute a large family of diverse and well-conserved genes, which encode transcription factors. [16][17][18] Members of this gene family are subdivided on a homology basis into ten groups (A to J), and SOX group F comprises the SOX 7, 17 and 18 genes. 17 SOX 18 is transiently expressed in the ...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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The lymphangiogenic factor SOX 18: A key indicator to stage gastric tumor progression

Eom¹,

Jo²,

Kook³

et al. 2011

Intl Journal of Cancer

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“…Sox7 belongs to the subgroup F, along with Sox17 and Sox18. Sox17 has been shown to be involved in cardiac and hematopoietic development in addition to definitive endoderm development (Liu et al, 2007;Kanai-Azuma et al, 2002;Sakamoto et al, 2007). Sox18 is important in blood vessel and lymphatic development in mice.…”

Section: Introductionmentioning

confidence: 99%

“…Sox17 -/-mouse mutants have defects in heart looping, cardiac bifida, and impaired cardiac mesoderm differentiation (Liu et al, 2007;Pfister et al, 2011;Sakamoto et al, 2007). Mutations in SOXF genes have also been reported in human diseases: SOX18 mutations cause hypotrichosis-lymphedema-telangiectasia syndrome, a congenital condition characterized by dilated veins, varicosities, and capillaries underneath transparent skin, and SOX17 mutations have been found in some cases of primary lymphedema (Francois et al, 2008;Irrthum et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Sox7 in vascular development: review, insights and potential mechanisms

Wat

Wat²

2014

Int. J. Dev. Biol.

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Cardiovascular development is crucial to the survival of higher organisms, integrally transporting oxygen and nutrients and in later life, facilitating immune function. Only in recent years has the molecular basis of the formation of this ancient conduit system been explored. While transcription factors are essential to specify and differentiate core cellular and structural components of the developing heart and vessels, only a subset of these essential factors are currently known. A transcription factor of emerging importance in the cardiovascular system is Sox7, a member of the F group of Sox genes, as Sox7 removal in recent animal and cellular studies has resulted in disruptions of cardiovascular development. However, the molecular mechanisms of Sox7 action have largely remained obscure. In this paper, we first review the highly conserved and robust cardiovascular expression pattern of Sox7 across multiple species. We then provide evidence of a compelling role for Sox7 in vascular development, elucidating major pathways in which Sox7 functions, including VEGF/Flk1 signaling, Wnt signaling, and Notch pathway. Furthermore, we propose mechanisms connecting all of these important developmental pathways through Sox7, in a way not previously postulated in the developing vascular system. The emerging picture reveals Sox7 as an important developmental gene that connects other vascular regulators and that has significance in human disease.

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Interactions between environmental factors and polymorphisms in angiogenesis pathway genes in esophageal adenocarcinoma risk: A case‐only study

Zhai

Zhao²,

Liu

et al. 2011

Cancer

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BACKGROUND Gastroesophageal reflux symptoms (GERD), higher body mass index (BMI), smoking, and genetic variants in angiogenic pathway genes have been individually associated with increased risk of esophageal adenocarcinoma (EA). However, how angiogenic gene polymorphisms and environmental factors jointly affect EA development remains unclear. METHODS Using a case-only design (n = 335), we examined interaction between 141 functional/tagging angiogenic SNPs and environmental factors (GERD, BMI, smoking) in modulating EA risk. Gene-environment interactions were assessed by a two-step approach. First, we applied random forest (RF) to screen for important SNPs that had either main or interaction effects. Second, we used case-only logistic regression (LR) to assess the effects of gene-environment interactions on EA risk, adjusting for covariates and false-discovery rate (FDR). RESULTS RF analyses identified three sets of SNPs (17 SNPs-GERD, 26 SNPs-smoking, and 34 SNPs-BMI) that had the highest importance scores. In subsequent LR analyses, interactions between 3 SNPs (rs2295778 of HIF1AN, rs133376 of TSC2, and rs2519757 of TSC1) and GERD, 2 SNPs (rs2295778 of HIF1AN, rs2296188 (VEGFR1) and smoking, and 7 SNPs (rs2114039 of PDGRFA, rs2296188 of VEGFR1, rs11941492 of VEGFR1, rs3756309 of PDGFRB, rs7324547 of VEGFR1, rs17619601 of VEGFR1, and rs17625898 of VEGFR1) and BMI were significantly associated with EA development (all FDR ≤0.10). Moreover, these interactions tended to have a SNP dose-response effects for increased EA risk with increasing number of combined risk genotypes. CONCLUSIONS These findings suggest that genetic variations in angiogenic genes may modify EA susceptibility through interactions with environmental factors in a SNP dose-response manner.

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Redundant roles of Sox17 and Sox18 in early cardiovascular development of mouse embryos

Cited by 162 publications

References 27 publications

The lymphangiogenic factor SOX 18: A key indicator to stage gastric tumor progression

The lymphangiogenic factor SOX 18: A key indicator to stage gastric tumor progression

Sox7 in vascular development: review, insights and potential mechanisms

Interactions between environmental factors and polymorphisms in angiogenesis pathway genes in esophageal adenocarcinoma risk: A case‐only study

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