Activin/Nodal signalling in stem cells

Pauklin, Siim; Vallier, Ludovic

doi:10.1242/dev.091769

Cited by 163 publications

(146 citation statements)

References 142 publications

Supporting

Mentioning

145

Contrasting

Order By: Relevance

“…Activin A, another member of the TGF-b family of ligands, is also expressed in bone and cartilage, and activates the Smad2-and Smad3-dependent pathway with potential overlap with TGF-b functions (Ogawa et al 1992;Massagué and Gomis 2006;Eijken et al 2007;Tsuchida et al 2009;Pauklin and Vallier 2015;Salazar et al 2016). …”

Section: Roles Of Tgf-b and Bmp Signaling In Bone Formation Skeletalmentioning

confidence: 99%

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

MacFarlane

Haupt

Dietz

et al. 2017

Cold Spring Harb Perspect Biol

View full text Add to dashboard Cite

The transforming growth factor b (TGF-b) family of signaling molecules, which includes TGF-bs, activins, inhibins, and numerous bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs), has important functions in all cells and tissues, including soft connective tissues and the skeleton. Specific TGF-b family members play different roles in these tissues, and their activities are often balanced with those of other TGF-b family members and by interactions with other signaling pathways. Perturbations in TGF-b family pathways are associated with numerous human diseases with prominent involvement of the skeletal and cardiovascular systems. This review focuses on the role of this family of signaling molecules in the pathologies of connective tissues that manifest in rare genetic syndromes (e.g., syndromic presentations of thoracic aortic aneurysm), as well as in more common disorders (e.g., osteoarthritis and osteoporosis). Many of these diseases are caused by or result in pathological alterations of the complex relationship between the TGF-b family of signaling mediators and the extracellular matrix in connective tissues.T he transforming growth factor b (TGF-b) family of cytokines comprises the three TGF-b proteins (TGF-b1, TGF-b2, and TGFb3) and related growth and differentiation factors such as activins, inhibins, bone morphogenic proteins (BMPs), and growth and differentiation factors (GDFs). These molecules play critical roles both in normal development and in several pathological conditions, including inflammation, fibrosis, and cancer (reviewed in Li and Flavell 2006;Gordon and Blobe 2008;Ikushima and Miyazono 2010). This review focuses on the role of these proteins in development and homeostasis of the skeleton and other connective tissues (summarized in Fig. 1) and on the diseases that ensue when these pathways are altered. Aberrant signaling in these pathways has been associated with common connective 6 These authors contributed equally to this work.

show abstract

Section: Roles Of Tgf-b and Bmp Signaling In Bone Formation Skeletalmentioning

confidence: 99%

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

MacFarlane

Haupt

Dietz

et al. 2017

Cold Spring Harb Perspect Biol

View full text Add to dashboard Cite

show abstract

“…One possible reason for such complexity resides in the recognized contextdependency of Nodal function (reviewed in [1,3]). 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].…”

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

View full text Add to dashboard Cite

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'.

show abstract

“…[13][14][15][16]19 As a member of the TGFβ superfamily, Nodal is best known for its critical role during embryogenesis, where it coordinates tissue organization, body axis specification, and maintains the pluripotency of human embryonic stem cells. [35][36][37] Previous studies from our laboratory have shown the potential for Nodal to function as a predictive and prognostic biomarker in melanoma and breast cancer. 16,17 Experimental evidence also shows that inhibition of Nodal signaling in several cancer models leads to decreases in tumorigenicity, metastasis, invasion, angiogenesis, and the plastic stem cell phenotype.…”

Section: Discussionmentioning

confidence: 99%

Targeting melanoma with front-line therapy does not abrogate Nodal-expressing tumor cells

Hendrix

Kandela

Mazar

et al. 2017

Laboratory Investigation

View full text Add to dashboard Cite

Metastatic melanoma is a highly aggressive skin cancer with a poor prognosis. It is the leading cause of skin cancer deaths with a median overall survival for advanced-stage metastatic disease of o6 months. Despite advances in the field with conventional and targeted therapies, the heterogeneity of melanoma poses the greatest ongoing challenge, ultimately leading to relapse and progression to a more drug-resistant tumor in most patients. Particularly noteworthy are recent findings, indicating that these therapies exert selective pressure on tumors resulting in the activation of pathways associated with cancer stem cells that are unresponsive to current therapy. Our previous studies have shown how Nodal, an embryonic morphogen of the transforming growth factor-beta superfamily, is one of these critical factors that is reactivated in aggressive melanoma and resistant to conventional chemotherapy, such as dacarbazine. In the current study, we sought to determine whether BRAF inhibitor (BRAFi) therapy targeted Nodal-expressing tumor cells in uniquely matched unresectable stage III and IV melanoma patient samples before and after therapy that preceded their eventual death due to disease. The results demonstrate that BRAFi treatment failed to affect Nodal levels in melanoma tissues. Accompanying experiments in soft agar and in nude mice showed the advantage of using combinatorial treatment with BRAFi plus anti-Nodal monoclonal antibody to suppress tumor growth and metastasis. These data provide a promising new approach using front-line therapy combined with targeting a cancer stem cell-associated molecule-producing a more efficacious response than monotherapy.

show abstract

Activin/Nodal signalling in stem cells

Cited by 163 publications

References 142 publications

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

Nodal signalling and asymmetry of the nervous system

Targeting melanoma with front-line therapy does not abrogate Nodal-expressing tumor cells

Contact Info

Product

Resources

About