Nodal promotes growth and invasion in human gliomas

Cc, Lee; Hj, Jan; Jh, Lai; Hi, Ma; Hueng, Dueng‐Yuan; Lee, Gary; Cheng, Yue; Lw, Liu; Wei, Hen-Wei; Hm, Lee

doi:10.1038/onc.2010.55

Cited by 94 publications

(90 citation statements)

References 33 publications

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“…31 In several types of cancer, the acquisition of Nodal expression is associated with increased tumorigenesis, invasion and metastasis. 2,6,[32][33][34] Endometrial stromal cells express the Activin/Nodal receptor subtypes ALK 4, ActRIIA, and ActRIIB with maximum levels in the early secretory phase, 35 but the potential functions of Nodal signaling in the endometrial stroma remain unknown. Extrapolation from its effects on embryogenesis suggests that Nodal stimulation induces the cells to adopt features as proliferation and migration, 11 which are key steps in the regeneration of the endometrium.…”

Section: Discussionmentioning

confidence: 99%

Expression of Nodal, Cripto, SMAD3, Phosphorylated SMAD3, and SMAD4 in the Proliferative Endometrium of Women With Endometriosis

et al. 2015

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Background: Nodal is a growth factor of the transforming growth factor b superfamily that is expressed in high turnover tissues, such as the human endometrium, and in several malignancies. The effects of Nodal are modulated by the coreceptor Cripto and mediated by SMAD proteins. This study evaluated the gene and protein expression of Nodal, Cripto, total and phosphorylated (p) SMAD3, and SMAD4 in the proliferative endometrium of women with and without endometriosis. Method: Total RNA was isolated and complementary DNA synthesized from eutopic endometrium of women with (n ¼ 15) and without (n ¼ 12) endometriosis, followed by quantitative real-time polymerase chain reaction (PCR) to evaluate the gene expression of Nodal, Cripto, SMAD3, and SMAD4. Western blot was used to evaluate the protein levels of Nodal and Cripto, and immunohistochemistry was performed to localize SMAD3, pSMAD3, and SMAD4. Results: Although Nodal expression was unchanged in women with endometriosis, real-time PCR indicated lower gene expression of Cripto (fold change 0.27, P < .05) in the endometriosis group. This difference, however, was not maintained at protein expression level as assessed by Western blot. The immunostaining of total SMAD3 was reduced in the endometriosis group (P < .01), but the localization of pSMAD3 and the nuclear staining of SMAD4 were unchanged. Conclusion: These findings suggest that the Nodal signaling pathway has subtle changes in the endometrium of women with endometriosis, but this imbalance may not cause functional damage as it seems not to affect the nuclear expression of SMAD4.

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Section: Discussionmentioning

confidence: 99%

Expression of Nodal, Cripto, SMAD3, Phosphorylated SMAD3, and SMAD4 in the Proliferative Endometrium of Women With Endometriosis

et al. 2015

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“…It is known, for example, that Nodal signalling can maintain pluripotency and prevent differentiation to neuroectoderm in human embryonic stem cells (hESC) and mouse epiblastderived stems cells (mEpiSC) [32] while it is necessary for endoderm differentiation in pluripotent cells and the mouse gastrula embryo [3,33]. Similarly, Nodal can inhibit cell migration, invasion and proliferation in human trophoblasts [34,35] while it promotes the opposite in human glioma and breast cancer cells [36,37]. Such divergent mechanisms create the necessity of developing a conceptual framework to help recognize L-R patterns and assess the phenomenon in a meaningful manner.…”

Section: Context-dependency Of Nodal Functions In Nervous System Asymmentioning

confidence: 99%

Nodal signalling and asymmetry of the nervous system

Signore

Palma

Concha

2016

Phil. Trans. R. Soc. B

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One contribution of 17 to a theme issue 'Provocative questions in left -right asymmetry'. The role of Nodal signalling in nervous system asymmetry is still poorly understood. Here, we review and discuss how asymmetric Nodal signalling controls the ontogeny of nervous system asymmetry using a comparative developmental perspective. A detailed analysis of asymmetry in ascidians and fishes reveals a critical context-dependency of Nodal function and emphasizes that bilaterally paired and midline-unpaired structures/organs behave as different entities. We propose a conceptual framework to dissect the developmental function of Nodal as asymmetry inducer and laterality modulator in the nervous system, which can be used to study other types of body and visceral organ asymmetries. Using insights from developmental biology, we also present novel evolutionary hypotheses on how Nodal led the evolution of directional asymmetry in the brain, with a particular focus on the epithalamus. We intend this paper to provide a synthesis on how Nodal signalling controls left-right asymmetry of the nervous system. This article is part of the themed issue 'Provocative questions in leftright asymmetry'.

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“…Nodal signals via a SMAD2/3-dependent pathway following activation of a receptor complex, including ALK4/7, ActRIIB, and the coreceptor Cripto-1 (8). Recent studies show that Nodal promotes a dedifferentiated phenotype in melanoma, glioma, prostate cancer, and pancreatic cancer and that it increases cancer cell invasion and tumorigenicity in these cancer types (5,7,9,10). Nodal expression is also correlated with breast cancer progression, such that Nodal is absent in normal breast tissues, yet is aberrantly expressed in invasive breast cancer lesions (6).…”

Section: Introductionmentioning

confidence: 99%

“…Nodal, a morphogen from the TGF-b superfamily, is a hESCassociated protein that becomes reexpressed during cancer progression (1,(5)(6)(7). Nodal signals via a SMAD2/3-dependent pathway following activation of a receptor complex, including ALK4/7, ActRIIB, and the coreceptor Cripto-1 (8).…”

Section: Introductionmentioning

confidence: 99%

Embryonic Protein Nodal Promotes Breast Cancer Vascularization

Quail

Walsh²,

Findlay³

et al. 2012

Cancer Research

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Tumor vascularization is requisite for breast cancer progression, and high microvascular density in tumors is a poor prognostic indicator. Patients bearing breast cancers expressing human embryonic stem cell (hESC)-associated genes similarly exhibit high mortality rates, and the expression of embryonic proteins is associated with tumor progression. Here, we show that Nodal, a hESC-associated protein, promotes breast cancer vascularization. We show that high levels of Nodal are positively correlated with high vascular densities in human breast lesions (P ¼ 0.0078). In vitro, we show that Nodal facilitates breast cancer-induced endothelial cell migration and tube formation, largely by upregulating the expression and secretion of proangiogenic factors by breast cancer cells. Using a directed in vivo angiogenesis assay and a chick chorioallantoic membrane assay, we show that Nodal promotes vascular recruitment in vivo. In a clinically relevant in vivo model, whereby Nodal expression was inhibited following tumor formation, we found a significant reduction in tumor vascularization concomitant with elevated hypoxia and tumor necrosis. These findings establish Nodal as a potential target for the treatment of breast cancer angiogenesis and progression. Cancer Res; 72(15); 3851-63. Ó2012 AACR.

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Nodal promotes growth and invasion in human gliomas

Cited by 94 publications

References 33 publications

Expression of Nodal, Cripto, SMAD3, Phosphorylated SMAD3, and SMAD4 in the Proliferative Endometrium of Women With Endometriosis

Expression of Nodal, Cripto, SMAD3, Phosphorylated SMAD3, and SMAD4 in the Proliferative Endometrium of Women With Endometriosis

Nodal signalling and asymmetry of the nervous system

Embryonic Protein Nodal Promotes Breast Cancer Vascularization

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