Restoring Tissue Homeostasis

Özhan, Günes; Weidinger, Gilbert

doi:10.1002/9781118444122.ch26

Cited by 6 publications

(3 citation statements)

References 106 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Wnt/β‐catenin (canonical Wnt) signaling is a key signaling pathway that controls cell fate determination during embryonic development, maintenance of tissue homeostasis, and regeneration [ 13 , 14 , 15 ]. Wnt/β‐catenin pathway is held in the inactive state in the absence of a canonical Wnt ligand, leading to phosphorylation and degradation of β‐catenin by a cytoplasmic multiprotein complex, termed the β‐catenin destruction complex, consisting of casein kinase 1α (Ck1α), glycogen synthase kinase 3β (Gsk3β), the tumor suppressors adenomatous polyposis coli (APC) and Axin, protein phosphatase 2A (PP2A) and the E3‐ubiquitin ligase β‐transducin repeats‐containing protein β‐TrCP [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Comparative membrane lipidomics of hepatocellular carcinoma cells reveals diacylglycerol and ceramide as key regulators of Wnt/β‐catenin signaling and tumor growth

Azbazdar,

Demirci,

Heger

et al. 2023

Molecular Oncology

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is largely associated with aberrant activation of Wnt/β‐catenin signaling. Nevertheless, how membrane lipid composition is altered in HCC cells with abnormal Wnt signaling remains elusive. Here, by exploiting comprehensive lipidome profiling, we unravel the membrane lipid composition of six different HCC cell lines with mutations in components of Wnt/β‐catenin signaling, leading to differences in their endogenous signaling activity. Among the differentially regulated lipids are diacylglycerol (DAG) and ceramide, which were downregulated at the membrane of HCC cells after Wnt3a treatment. DAG and ceramide enhanced Wnt/β‐catenin signaling by inducing caveolin‐mediated endocytosis of the canonical Wnt‐receptor complex, while their depletion suppressed the signaling activity along with a reduction of caveolin‐mediated endocytosis in SNU475 and HepG2 cells. Moreover, depletion of DAG and ceramide significantly impeded the proliferation, tumor growth, and in vivo migration capacity of SNU475 and HepG2 cells. This study, by pioneering plasma membrane lipidome profiling in HCC cells, exhibits the remarkable potential of lipids to correct dysregulated signaling pathways in cancer and stop abnormal tumor growth.

show abstract

Section: Introductionmentioning

confidence: 99%

Comparative membrane lipidomics of hepatocellular carcinoma cells reveals diacylglycerol and ceramide as key regulators of Wnt/β‐catenin signaling and tumor growth

Azbazdar,

Demirci,

Heger

et al. 2023

Molecular Oncology

View full text Add to dashboard Cite

show abstract

“…Owing to its key roles in the development and growth of tissues and organs involved in the regulation of metabolism, Wnt signaling, in particular, the β-catenin pathway (also termed the canonical Wnt pathway) has been associated with a range of metabolic diseases including obesity and NAFLD (Karabicici et al, 2021). Moreover, Wnt/β-catenin signaling plays key roles in the activation of tissue repair mechanisms in a broad range of regenerating tissues and organs studied to date (Whyte et al, 2012; Ozhan and Weidinger, 2014; Ozhan and Weidinger, 2015). Parts of the central nervous system (CNS) including the retina, optic tectum, and spinal cord have been deciphered to activate Wnt signaling to mediate proliferation and differentiation of stem/progenitor cells in response to injury in the adult zebrafish (Meyers et al, 2012; Briona et al, 2015; Shi et al, 2015; Wehner et al, 2017; Shimizu et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

High-fat diet feeding triggers a regenerative response in the adult zebrafish brain

Azbazdar

Poyraz

Ozalp

et al. 2022

Preprint

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) includes a range of liver conditions ranging from excess fat accumulation to liver failure. NAFLD is strongly associated with high-fat diet (HFD) consumption that constitutes a metabolic risk factor. While HFD has been elucidated concerning its several systemic effects, there is little information about its influence on the brain at the molecular level. Here, by using a high-fat diet (HFD)-feeding of adult zebrafish, we first reveal that excess fat uptake results in weight gain and fatty liver. Prolonged exposure to HFD induces a significant increase in the expression of pro-inflammation, apoptosis, and proliferation markers in the liver and brain tissues. Immunofluorescence analyses of the brain tissues disclose stimulation of apoptosis and widespread activation of glial cell response. Moreover, glial activation is accompanied by an initial decrease in the number of neurons and their subsequent replacement in the olfactory bulb and the telencephalon. Long-term consumption of HFD causes activation of Wnt/Beta-catenin signaling in the brain tissues. Finally, fish fed an HFD induces anxiety, and aggressiveness and increases locomotor activity. Thus, HFD feeding leads to a non-traumatic brain injury and stimulates a regenerative response. The activation mechanisms of a regeneration response in the brain can be exploited to fight obesity and recover from non-traumatic injuries.

show abstract

“…Wnt/β-catenin signaling, the so-called canonical Wnt pathway, regulates a broad range of biological processes during embryonic development, adult tissue homeostasis and tissue regeneration (Huang and He, 2008; Clevers and Nusse, 2012; Ozhan and Weidinger, 2014). Aberrant Wnt signaling is related to various types of cancer, congenital defects and degenerative diseases (Logan and Nusse, 2004; Clevers, 2006; Nusse and Clevers, 2017).…”

Section: Introductionmentioning

confidence: 99%

More Favorable Palmitic Acid Over Palmitoleic Acid Modification of Wnt3 Ensures Its Localization and Activity in Plasma Membrane Domains

Azbazdar

Ozalp

Sezgin

et al. 2019

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

While the lateral organization of plasma membrane components has been shown to control binding of Wnt ligands to their receptors preferentially in the ordered membrane domains, the role of posttranslational lipid modification of Wnt on this selective binding is unknown. Here, we identify that the canonical Wnt is presumably acylated by palmitic acid, a saturated 16-carbon fatty acid, at a conserved serine residue. Acylation of Wnt3 is dispensable for its secretion and binding to Fz8 while it is essential for Wnt3's proper binding and domain-like diffusion in the ordered membrane domains. We further unravel that non-palmitoylated Wnt3 is unable to activate Wnt/β-catenin signaling either in zebrafish embryos or in mammalian cells. Based on these results, we propose that the lipidation of canonical Wnt, presumably by a saturated fatty acid, determines its competence in interacting with the receptors in the appropriate domains of the plasma membrane, ultimately keeping the signaling activity under control.

show abstract

Restoring Tissue Homeostasis

Cited by 6 publications

References 106 publications

Comparative membrane lipidomics of hepatocellular carcinoma cells reveals diacylglycerol and ceramide as key regulators of Wnt/β‐catenin signaling and tumor growth

Comparative membrane lipidomics of hepatocellular carcinoma cells reveals diacylglycerol and ceramide as key regulators of Wnt/β‐catenin signaling and tumor growth

High-fat diet feeding triggers a regenerative response in the adult zebrafish brain

More Favorable Palmitic Acid Over Palmitoleic Acid Modification of Wnt3 Ensures Its Localization and Activity in Plasma Membrane Domains

Contact Info

Product

Resources

About