Nodal protein processing and fibroblast growth factor 4 synergize to maintain a trophoblast stem cell microenvironment

Guzman-Ayala, Marcela; Ben-Haim, Nadav; Beck, Séverine; Constam, Daniel

doi:10.1073/pnas.0405429101

Cited by 145 publications

(126 citation statements)

References 21 publications

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“…and inducing apoptosis in human trophoblast cells. 24,36 Based on these evidences, we proposed that NOMO1 might be functionally involved in trophoblast cell growth regulation by miR-675.…”

Section: Discussionmentioning

confidence: 99%

The imprinted H19 gene regulates human placental trophoblast cell proliferation via encoding miR-675 that targets Nodal Modulator 1 (NOMO1)

et al. 2012

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“…and inducing apoptosis in human trophoblast cells. 24,36 Based on these evidences, we proposed that NOMO1 might be functionally involved in trophoblast cell growth regulation by miR-675.…”

Section: Discussionmentioning

confidence: 99%

The imprinted H19 gene regulates human placental trophoblast cell proliferation via encoding miR-675 that targets Nodal Modulator 1 (NOMO1)

et al. 2012

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“…This signaling axis also plays a role in the maintenance of pluripotency in the epiblast and trophectoderm compartments [27,57]. During early mouse embryogenesis, Nodal exhibits a dynamic expression pattern that lasts until mid gestation.…”

Section: Function and Expression Of Cripto-1 And Nodal During Embryonmentioning

confidence: 99%

Emerging Roles of Nodal and Cripto-1: From Embryogenesis to Breast Cancer Progression

Strizzi

Postovit

Margaryan

et al. 2008

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Breast carcinoma cells and embryonic progenitors similarly implement stem cell-associated signaling pathways to sustain continued growth and plasticity. Indeed, recent studies have implicated signaling pathways, including those associated with the Notch, and Transforming Growth Factor-Beta (TGF-β) superfamilies, as instrumental to both embryological development and breast cancer progression. In particular, Nodal, an embryonic morphogen belonging to the TGF-β superfamily, and its co-receptor, Cripto-1, are requisite to both embryogenesis and mammary gland maturation. Moreover, these developmental proteins have been shown to promote breast cancer progression. Here, we review the role of Nodal and its co-receptor Cripto-1 during development and we describe how this signaling pathway may be involved in breast cancer tumorigenesis. Moreover, we emphasize the potential utility of this signaling pathway as a novel target for the treatment and diagnosis of breast cancer.

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“…8 Nodal also acts on extraembryonic stem cells to inhibit precocious differentiation of trophoblast stem cells. 9 In the human placenta, expression of Nodal and ALK7 has previously been reported. 10 We demonstrated that Nodal, signaling through ALK7, inhibits trophoblast proliferation and induces apoptosis.…”

mentioning

confidence: 99%

Nodal Signals through Activin Receptor-Like Kinase 7 to Inhibit Trophoblast Migration and Invasion

Nadeem

Munir

et al. 2011

The American Journal of Pathology

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Trophoblast cell invasion into the uterus is an essential process for successful pregnancy, and shallow invasion of trophoblasts into the maternal decidua is linked to preeclampsia. We have reported that Nodal, a member of the transforming growth factor-␤ superfamily, acts through activin receptor-like kinase 7 (ALK7) to inhibit trophoblast proliferation and to induce apoptosis. In this study, we examined the spatial and temporal expression patterns of Nodal and ALK7 in human placenta from normal and preeclamptic pregnancies and investigated whether Nodal regulated trophoblast migration and invasion. Nodal and ALK7 were detected in villous and extravillous trophoblast cell populations in early gestation, and their levels were strongly up-regulated in preeclamptic placenta. Overexpression of Nodal or constitutively active ALK7 decreased cell migration and invasion, whereas knockdown of Nodal and ALK7 had the opposite effects. In placental explant culture, treatment with Nodal inhibited trophoblast outgrowth, whereas Nodal small-interfering RNA strongly induced the expansion of explants and the migration of extravillous trophoblast cells. Nodal stimulated the secretion of tissue inhibitor of metalloproteinase-1 and inhibited matrix metalloproteinase (MMP)-2 and MMP-9 activity. These findings suggest that the Nodal/ALK7 pathway plays important roles in human placentation and that its abnormal signaling may contribute to the development of preeclampsia.

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Nodal protein processing and fibroblast growth factor 4 synergize to maintain a trophoblast stem cell microenvironment

Cited by 145 publications

References 21 publications

The imprinted H19 gene regulates human placental trophoblast cell proliferation via encoding miR-675 that targets Nodal Modulator 1 (NOMO1)

The imprinted H19 gene regulates human placental trophoblast cell proliferation via encoding miR-675 that targets Nodal Modulator 1 (NOMO1)

Emerging Roles of Nodal and Cripto-1: From Embryogenesis to Breast Cancer Progression

Nodal Signals through Activin Receptor-Like Kinase 7 to Inhibit Trophoblast Migration and Invasion

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