Wnt signalling and the control of cellular metabolism

Abstract

At the cellular level, the biological processes of cell proliferation, growth arrest, differentiation and apoptosis are all tightly coupled to appropriate alterations in metabolic status. In the case of cell proliferation, this requires redirecting metabolic pathways to provide the fuel and basic components for new cells. Ultimately, the successful co-ordination of cell-specific biology with cellular metabolism underscores multicellular processes as diverse as embryonic development, adult tissue remodelling and cancer cell biology. The Wnt signalling network has been implicated in all of these areas. While each of the Wnt-dependent signalling pathways are being individually delineated in a range of experimental systems, our understanding of how they integrate and regulate cellular metabolism is still in its infancy. In the present review we reassess the roles of Wnt signalling in functionally linking cellular metabolism to tissue development and function.

Regulation of CXCL12 expression by canonical Wnt signaling in bone marrow stromal cells

“…The Wnt secreted proteins of molecular weight ~40kd are a family of glycosylated-lipid-modified proteins which are powerful regulators of embryonic development, cell differentiation, and proliferation (Logan andNusse, 2004, Sethi andVidal-Puig, 2010). Two distinct Wnt signaling pathways, the β-catenin-dependent canonical pathway and the β-catenin-independent so-called "noncanonical" pathway, including the Wnt/planar cell polarity pathway and the Wnt/Ca 2+ pathway, have been described.…”

“…The other class is the "noncanonical" Wnts such as Wnt5a and Wnt11 which act independently of or inhibit β-catenin signaling (Logan and Nusse, 2004). According to the model of canonical Wnt action, in cells lacking a Wnt signal, glycogen synthase kinase (GSK) -3β phosphorylates β-catenin, inducing rapid degradation of β-catenin via the ubiquitin-proteasome pathway (MacDonald et al, 2009, Sethi andVidal-Puig, 2010). Canonical Wnt signaling causes stabilization of β-catenin which then translocates to the nucleus, where it interacts with the transcription factors that regulate expression of several target genes including c-myc and osteoprotegerin (OPG) (MacDonald et al, 2009, Sato et al, 2009).…”

Role of WNT pathway in the determination of human mesenchymal stem cells into preadipocytes

“…In contrast to the detailed understanding of the canonical pathway, at present, non-canonical WNT signalling is poorly defined. At least two different non-canonical cascades exist (Sethi & Vidal-Puig 2010). In the WNT-cGMP/ Ca 2C pathway, specific WNT molecules and FZ isoforms trigger an intracellular Ca 2C release through activation of a heterotrimeric GTP-binding protein.…”

Wnt/?-Catenin Signalling during Liver Metabolism, Chronic Liver Disease and Hepatocarcinogenesis

“…To manage fluctuating metabolic demands, hepatic cells constantly alter the expression of respective regulatory pathways. Accordingly, hepatic Wnt signalling activity is modified under different physiological and pathophysiological conditions (45). In adult healthy hepatocytes, β-catenin is ubiquitously expressed, but it is more active in pericentral compared to periportal hepatocytes (44).…”

“…In this case, β-catenin is able to bind and activate downstream signalling (Figure 2) (40). It has been estimated that Wnt/β-catenin signalling regulates the expression of more than 80 target genes involved in cell fate determination, development, regeneration, zonation, metabolism, fibrosis and carcinogenesis of the liver (44,45). The canonical Wnt/β-catenin pathway.…”