Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik

Permanent URI for this collectionhttps://hdl.handle.net/11147/9

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Access type: Open accessAuthor: search.filters.author.Azbazdar, Yağmur

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  • Article
    Citation - WoS: 7
    Citation - Scopus: 6
    Addition of Exogenous Diacylglycerol Enhances Wnt/Β-catenin Signaling Through Stimulation of Macropinocytosis
    (Elsevier, 2023) Azbazdar, Yağmur; Tejeda-Munoz, Nydia; Monka, Julia C.; Dayrit, Alex; Binder, Grace; De Robertis, Edward M.; Özhan, Güneş
    Activation of Wnt signaling triggers macropinocytosis and drives many tumors. We now report that the exogenous addition of the second messenger lipid sn-1,2 DAG to the culture medium rapidly induces macropinocytosis. This is accompanied by potentiation of the effects of added Wnt3a recombinant protein or the glycogen synthase kinase 3 (GSK3) inhibitor lithium chloride (LiCl, which mimics Wnt signaling) in luciferase transcriptional reporter assays. In a colorectal carcinoma cell line in which mutation of adenomatous polyposis coli (APC) causes constitutive Wnt signaling, DAG addition increased levels of nuclear β-catenin, and this increase was partially inhibited by an inhibitor of macropinocytosis. DAG also expanded multivesicular bodies marked by the tetraspan protein CD63. In an in vivo situation, microinjection of DAG induced Wnt-like twinned body axes when co-injected with small amounts of LiCl into Xenopus embryos. These results suggest that the DAG second messenger plays a role in Wnt-driven cancer progression. © 2023 The Author(s)
  • Article
    Citation - WoS: 14
    Citation - Scopus: 14
    Comparative Membrane Lipidomics of Hepatocellular Carcinoma Cells Reveals Diacylglycerol and Ceramide as Key Regulators of Wnt/Β-catenin Signaling and Tumor Growth
    (Wiley, 2023) Heger, Guillaume; Azbazdar, Yağmur; Demirci, Yeliz; İpekgil, Doğaç; Karabiçici, Mustafa; Özhan, Güneş
    Hepatocellular carcinoma (HCC) is largely associated with aberrant activation of Wnt/beta-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/beta-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/b-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.
  • Article
    Citation - WoS: 7
    Citation - Scopus: 8
    High-Fat Diet Feeding Triggers a Regenerative Response in the Adult Zebrafish Brain
    (Springer, 2023) Azbazdar, Yağmur; Poyraz, Yusuf Kaan; Özalp, Özgün; Nazlı, Dilek; İpekgil, Doğaç; Cucun, GÖkhan; Özhan, Güneş
    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/β-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.