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

Abstract

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.

Nodal enhances the activity of FoxO3a and its synergistic interaction with Smads to regulate cyclin G2 transcription in ovarian cancer cells

“…Recently, we have shown that Nodal and its receptors, activin receptor-like kinase 7 (ALK7) and ALK4, are expressed in human ovarian cancer cells . Furthermore, Nodal was also detected in rat ovarian follicular cells, normal and malignant human endometrial cells (Papageorgiou et al, 2009), lactating mammary (Kenney et al, 2004) and breast cancer cells (Strizzi et al, 2008), as well as islet cells in the pancreas (Zhang et al, 2008). The expression of Nodal in a variety of tissues suggests the extension of its biological function beyond embryo development.…”

Lefty inhibits glioma growth by suppressing Nodal-activated Smad and ERK1/2 pathways

“…Over-expression of Nodal in poorly-invasive cell lines in vitro led to an increased aggressiveness, while knocking-down Nodal in highlyinvasive cell lines exhibited an opposite effect. Many recent studies have proven the promoting effect of Nodal on tumor growth [12][13][14][15]. Lee et al [11] showed that Nodal over-expression increased the secretion of MMP-2, enhanced cell invasiveness, and promoted cell proliferation in vitro, as well as increased tumor growth in vivo.…”

Netrin-1: Just an axon-guidance factor?

“…Netrin-1 appears to be primarily expressed in regions of tissue remodelling rather than in quiescent tissue (Strizzi et al 2008). Interestingly, the ovarian follicle is a typical site of differentiation and reorganization 70 KD Fig.…”