Inhibition of FNDC1 suppresses gastric cancer progression by interfering with Gβγ-VEGFR2 complex formation

Lu, Yen‐Shen; Huang, Panpan; Zeng, Xiangwu; Liu, Wenyu; Zhao, Rui; Li, Jing; Cao, Gaolu; Hu, Yue; Xiao, Qin; Wang, Meng; Huang, Weicai; Tang, Xuerui; Liu, Xiaojian; Wei, Hulai

doi:10.1016/j.isci.2023.107534

Cited by 4 publications

(1 citation statement)

References 40 publications

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“…The RNA-Seq expression data and clinical pathological parameters of GC patients were downloaded from the Cancer Genome Atlas (TCGA) ( http://cancergenome.nih.gov/ ) database. The gene expression and the survival rate were analyzed as described previously 33 .…”

Section: Methodsmentioning

confidence: 99%

RNA demethylase FTO participates in malignant progression of gastric cancer by regulating SP1-AURKB-ATM pathway

Zeng,

Lu,

Zeng

et al. 2024

Commun Biol

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Gastric cancer (GC) is the 5th most prevalent cancer and the 4th primary cancer-associated mortality globally. As the first identified m6A demethylase for removing RNA methylation modification, fat mass and obesity-associated protein (FTO) plays instrumental roles in cancer development. Therefore, we study the biological functions and oncogenic mechanisms of FTO in GC tumorigenesis and progression. In our study, FTO expression is obviously upregulated in GC tissues and cells. The upregulation of FTO is associated with advanced nerve invasion, tumor size, and LNM, as well as the poor prognosis in GC patients, and promoted GC cell viability, colony formation, migration and invasion. Mechanistically, FTO targeted specificity protein 1 and Aurora Kinase B, resulting in the phosphorylation of ataxia telangiectasia mutated and P38 and dephosphorylation of P53. In conclusion, the m6A demethylase FTO promotes GC tumorigenesis and progression by regulating the SP1-AURKB-ATM pathway, which may highlight the potential of FTO as a diagnostic biomarker for GC patients’ therapy response and prognosis.

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Section: Methodsmentioning

confidence: 99%

RNA demethylase FTO participates in malignant progression of gastric cancer by regulating SP1-AURKB-ATM pathway

Zeng,

Lu,

Zeng

et al. 2024

Commun Biol

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Non-canonical G protein signaling

Nürnberg,

Beer-Hammer,

Reisinger

et al. 2024

Pharmacology & Therapeutics

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FNDC1 Competitively Binds Gβ2 to Suppress the β-Catenin Destruction Complex and Enhance Wnt Signaling Pathway Activation

Jiang,

Chen,

Lin

et al. 2024

Preprint

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Background: Elevated FNDC1 expression in gastric cancer (GC) cells activates the Wnt/β-catenin pathway, contributing to their malignant traits. However, the exact mechanism governing this process remains unclear. Methods: Bioinformatics analyses were used to identify the expression of FDNC1 in pan-cancer, its correlation with clinical outcomes, and biological functions in GC. Co-immunoprecipitation assays and western blot elucidate the interaction between FDNC1 and Gβ2/Gγ2 and the expression of Axin1, GSK3β, APC, and Dvl. The specific binding sites of FNDC1 and Gβ2 were explored by co-immunoprecipitation. Results: FNDC1 was highly expressed in GC tissue, and its expression level is positively correlated with poor prognosis of GC. Functional enrichment analysis shows that FNDC1-related genes may participate in regulating the Wnt signaling pathway. In vitro assays prove that FNDC1 competitively binds to the Gβ2 protein. This binding caused Dvl to separate from Gβγ. Subsequently, Dvl was released and recruited Axin1, facilitating the degradation of Axin1 and activating the Wnt/β-catenin signaling pathway. We further identified the WD5 amino acid segment (residues 224-254) as the specific binding region of FNDC1 on Gβ2. Discussion: This study reveals a novel mechanism where FNDC1 competitively binds Gβ2, inhibiting β-catenin degradation and enhancing the Wnt/β-catenin signaling pathway.

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Inhibition of FNDC1 suppresses gastric cancer progression by interfering with Gβγ-VEGFR2 complex formation

Cited by 4 publications

References 40 publications

RNA demethylase FTO participates in malignant progression of gastric cancer by regulating SP1-AURKB-ATM pathway

RNA demethylase FTO participates in malignant progression of gastric cancer by regulating SP1-AURKB-ATM pathway

Non-canonical G protein signaling

FNDC1 Competitively Binds Gβ2 to Suppress the β-Catenin Destruction Complex and Enhance Wnt Signaling Pathway Activation

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