Wnt/β-Catenin Mediates AICAR Effect to Increase GATA3 Expression and Inhibit Adipogenesis

Wang, Li; Di, Lijun

doi:10.1074/jbc.m115.641332

Cited by 36 publications

(27 citation statements)

References 53 publications

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“…S4). Therefore, we evaluated the correlation between AMPK and ECHS1, which has been previously reported to regulate GATA3 transcription (33) and whose level is decreased in ccRCC 3, as confirmed in this study by IHC ( Fig. 3D; Supplementary Fig.…”

Section: Ampk Regulates Echs1 Through Gata3supporting

confidence: 68%

Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth

et al. 2020

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The tumorigenic role and underlying mechanisms of lipid accumulation, commonly observed in many cancers, remain insufficiently understood. In this study, we identified an AMP-activated protein kinase (AMPK)-GATA-binding protein 3 (GATA3)enoyl-CoA hydratase short-chain 1 (ECHS1) pathway that induces lipid accumulation and promotes cell proliferation in clear cell renal cell carcinoma (ccRCC). Decreased expression of ECHS1, which is responsible for inactivation of fatty acid (FA) oxidation and activation of de novo FA synthesis, positively associated with ccRCC progression and predicted poor patient survival. Mechanistically, ECHS1 downregulation induced FA and branched-chain amino acid (BCAA) accumulation, which inhibited AMPK-promoted expression of GATA3, a transcriptional activator of ECHS1. BCAA accumulation induced activation of mTORC1 and de novo FA synthesis, and promoted cell proliferation. Furthermore, GATA3 expression phenocopied ECHS1 in predicting ccRCC progression and patient survival. The AMPK-GATA3-ECHS1 pathway may offer new therapeutic approaches and prognostic assessment for ccRCC in the clinic. Significance: These findings uncover molecular mechanisms underlying lipid accumulation in ccRCC, suggesting the AMPK-GATA3-ECHS1 pathway as a potential therapeutic target and prognostic biomarker.

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Section: Ampk Regulates Echs1 Through Gata3supporting

confidence: 68%

Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth

et al. 2020

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“…β-catenin was a multifunctional protein which had the dual activity of mediating cell adhesion and signal transduction [ 29 , 30 ]. After accumulation in the nucleus, β-catenin would form a transcription factor complex with the transcription factor TCF/LEF through its C-terminal transcriptional activator binding site, thereby facilitating the transcription of downstream target genes such as CyclinDl and e-mys [ 31–33 ]. In the present study, we observed that FOXF2 could suppress the expression level of β-catenin in the nucleus and target genes expression in the Wnt/β-catenin signaling pathway, such as c-Myc, CyclinDl, MMP9, and Lgr5.…”

Section: Discussionmentioning

confidence: 99%

FOXF2 inhibits proliferation, migration, and invasion of Hela cells by regulating Wnt signaling pathway

Zhang

Sang

et al. 2018

Bioscience Reports

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This article was aimed to study the FOXF2 effects on cervical cancer. Tumor tissues and adjacent tissues of 41 cervical cancer patients were collected. Human endometrial epithelial cells (hEEC) and Hela cells were cultured. FOXF2 expression vector and its empty vector were transfected into Hela cells, and named as pcDNA 3.1-FOXF2 group and Vector group, respectively. Hela cells without any treatment were set as Blank group. qRT-PCR was used to detect mRNA expression. Nude mouse xenograft assay was performed to test Hela cells proliferation ability in vivo. FOXF2 and β-catenin positive cell numbers were detected by immunohistochemistry. Protein expression was analyzed by Western blot. Cells migration and invasion were conducted by Transwell. Tumor tissues and Hela cells FOXF2 expression were lower than that in adjacent tissues and hEEC (P<0.01). Low FOXF2 expression predicted poor outcomes of cervical cancer patients. Compared with Blank group and Vector group, Hela cells of pcDNA 3.1-FOXF2 group were with higher FOXF2 expression, lower OD495 value, migrated and invaded cells, higher E-cadherin expression, lower Vimentin and Snail expression, smaller tumor volume in nude mice, lower c-Myc, CyclinDl, MMP9, Lgr5, and nuclear β-catenin expression (all P<0.01). FOXF2 inhibits Hela cells proliferation, migration, and invasion through regulating Wnt signaling pathway.

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“…32) Moreover, there are several reports showing that direct pharmacological activation of AMPK inhibits adipogenesis. 33,34) Collectively, our results suggest that gallic acid is a major bioactive component in FPE, and it exerts potent anti-obesity effects in vivo and in vitro through AMPK activation. A couple of recent studies have also reported beneficial effects of gallic acid on high fat diet-induced obesity, but the underlying mechanisms including changes in genes expression involved in fatty acid synthesis are yet to be fully elucidated.…”

Section: Discussionmentioning

confidence: 66%

Anti-obesity Effect of Fermented Persimmon Extracts <i>via</i> Activation of AMP-Activated Protein Kinase

Song

Yang

Hoa

et al. 2020

Biological & Pharmaceutical Bulletin

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There is significant cultivation of persimmon (Diospyros kaki) in East Asia, a plant whose fruit has abundant nutrients, including vitamins, polyphenols, and dietary fiber. Persimmon dietary supplements can benefit health by amelioration of diabetes, cardiovascular disease, and obesity. There are also persimmonbased beverages produced via fermentation, such as wines and vinegars, and increasing consumption of these products in East Asia. Although there is great interest in functional foods, the health effects of fermented persimmon extract (FPE) are completely unknown. We examined the effects of FPE on the metabolic parameters of mice fed a high-fat diet (HFD). Our results indicated that FPE supplementation led to an approx. 15% reduction of body weight, reduced abdominal and liver fat, and reduced serum levels of triglycerides, total cholesterol, and glucose. FPE also blocked the differentiation of murine 3T3-L1 pre-adipocyte cells into mature adipocytes. We suggest that gallic acid is a major bioactive component of FPE, and that AMPactivated protein kinase mediates the beneficial effects of FPE and gallic acid.

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Wnt/β-Catenin Mediates AICAR Effect to Increase GATA3 Expression and Inhibit Adipogenesis

Cited by 36 publications

References 53 publications

Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth

Inactivation of the AMPK–GATA3–ECHS1 Pathway Induces Fatty Acid Synthesis That Promotes Clear Cell Renal Cell Carcinoma Growth

FOXF2 inhibits proliferation, migration, and invasion of Hela cells by regulating Wnt signaling pathway

Anti-obesity Effect of Fermented Persimmon Extracts <i>via</i> Activation of AMP-Activated Protein Kinase

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