The lipid metabolism gene FTO influences breast cancer cell energy metabolism via the PI3K/AKT signaling pathway

Liu, Yazhuo; Wang, Ruoyu; Zhang, Lichuan; Li, Jianhua; Lou, Keli; Shi, Bingyin

doi:10.3892/ol.2017.6038

Cited by 74 publications

(59 citation statements)

References 21 publications

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“…Indeed, the FTO gene variant related to cancer risk is unlikely independent of adiposity ( 100 ). In addition, it was reported that by targeting the PI3K/AKT signaling, FTO influences breast cancer cell energy metabolism including lactic acid, ATP, pyruvate kinase activity, and hexokinase activity ( 79 ).…”

Section: Discussionmentioning

confidence: 99%

Critical Enzymatic Functions of FTO in Obesity and Cancer

et al. 2018

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Fat mass and obesity-associated protein (FTO) single-nucleotide polymorphisms (SNPs) have been linked to increased body mass and obesity in humans by genome-wide association studies (GWAS) since 2007. Although some recent studies suggest that the obesity-related SNPs in FTO influence obesity susceptibility likely through altering the expression of the adjacent genes such as IRX3 and RPGRIP1L, rather than FTO itself, a solid link between the SNP risk genotype and the increased FTO expression in both human blood cells and fibroblasts has been reported. Moreover, multiple lines of evidence have demonstrated that FTO does play a critical role in the regulation of fat mass, adipogenesis, and body weight. Epidemiology studies also showed a strong association of FTO SNPs and overweight/obesity with increased risk of various types of cancers. As the first identified messenger RNA N6-methyladenosine (m6A) demethylase, FTO has been shown recently to play m6A-dependent roles in adipogenesis and tumorigenesis (especially in the development of leukemia and glioblastoma). Given the critical roles of FTO in cancers, the development of selective and effective inhibitors targeting FTO holds potential to treat cancers. This mini review discusses the roles and underlying molecular mechanisms of FTO in both obesity and cancers, and also summarizes recent advances in the development of FTO inhibitors.

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Section: Discussionmentioning

confidence: 99%

Critical Enzymatic Functions of FTO in Obesity and Cancer

et al. 2018

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“…PI3K/Akt pathway is associated with characteristics of carcinogenesis and is frequently activated in numerous human cancer types, such as in non-small cell lung cancer [ 46 ], colorectal cancer [ 47 ], breast cancer [ 48 ] and prostate cancer [ 49 ]. In addition, a recent study showed that women with CC commonly display PI3K pathway alterations, indicating its potential value in the treatment of advanced and metastatic disease [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

SKA3 promotes cell proliferation and migration in cervical cancer by activating the PI3K/Akt signaling pathway

Wang

Niu

et al. 2018

Cancer Cell Int

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BackgroundCervical cancer (CC) is one of the most common cancers among females worldwide. Spindle and kinetochore-associated complex subunit 3 (SKA3), located on chromosome 13q, was identified as a novel gene involved in promoting malignant transformation in cancers. However, the function and underlying mechanisms of SKA3 in CC remain unknown. Using the Oncomine database, we found that expression of SKA3 mRNA is higher in CC tissues than in normal tissues and is linked with poor prognosis.MethodsIn our study, immunohistochemistry showed increased expression of SKA3 in CC tissues. The effect of SKA3 on cell proliferation and migration was evaluated by CCK8, clone formation, Transwell and wound-healing assays in HeLa and SiHa cells with stable SKA3 overexpression and knockdown. In addition, we established a xenograft tumor model in vivo.ResultsSKA3 overexpression promoted cell proliferation and migration and accelerated tumor growth. We further identified that SKA3 is involved in regulating cell cycle progression and the PI3K/Akt signaling pathway via RNA-sequencing (RNA-Seq) and gene set enrichment analyses. Western blotting results revealed that SKA3 overexpression increased levels of p-Akt, cyclin E2, CDK2, cyclin D1, CDK4, E2F1 and p-Rb in HeLa cells. Additionally, the use of an Akt inhibitor (GSK690693) significantly reversed the cell proliferation capacity induced by SKA3 overexpression in HeLa cells.ConclusionsWe suggest that SKA3 overexpression contributes to CC cell growth and migration by promoting cell cycle progression and activating the PI3K–Akt signaling pathway, which may provide potential novel therapeutic targets for CC treatment.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0670-4) contains supplementary material, which is available to authorized users.

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“…Mechanically, in our results, the phosphorylation of PI3K and AKT was inhibited by Mn12Ac. Previous studies reported that BRD4, FTO, and MACC1 could positively regulate the phosphorylation of PI3K and AKT, and miR‐200a and miR‐200b could negatively regulate the levels of p‐PI3K and p‐AKT . Whether Mn12Ac inhibited the phosphorylation of PI3K and AKT by regulating the above genes or other downstream genes should be the subject of future studies.…”

Section: Discussionmentioning

confidence: 93%

Manganese‐12 acetate suppresses the migration, invasion, and epithelial–mesenchymal transition by inhibiting Wnt/β‐catenin and PI3K/AKT signaling pathways in breast cancer cells

Xing

et al. 2018

Thoracic Cancer

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BackgroundBreast cancer is the leading cause of cancer‐related death in the world, and it is of great value to reveal the molecular mechanisms of breast cancer progression and develop new therapeutic targets.MethodsTranswell assay is used to analyze the migration and invasion of breast cancer cells. Real‐time PCR and western blotting assay are applied to detect the expression levels of epithelial–mesenchymal transition markers and the key members of Wnt/β‐catenin and PI3K/AKT signaling pathways.ResultsManganese‐12 acetate (Mn12Ac) significantly inhibited the migration and invasion of MCF7 and MDA‐MB‐231 breast cancer cells. Western blotting assay further showed that Mn12Ac significantly upregulated E‐cadherin, and downregulated N‐cadherin and vimentin. We further found that Mn12Ac reduced the mRNA expressions of epithelial–mesenchymal transition‐associated transcription factors snail, slug, twist1, and ZEB1 using real‐time PCR assay. Importantly, we further found that Mn12Ac significantly reduced the Wnt1 and β‐catenin protein expressions, and suppressed the phosphorylation of PI3K and AKT in MCF7 and MDA‐MB‐231 breast cancer cells. Very interestingly, we also showed that Mn12Ac decreased the mRNA and protein expressions of programmed cell death ligand 1.ConclusionTaken together, our results suggested that Mn12Ac inhibited the migration, invasion, and epithelial–mesenchymal transition by regulating Wnt/β‐catenin and PI3K/AKT signaling pathways in breast cancer.

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The lipid metabolism gene FTO influences breast cancer cell energy metabolism via the PI3K/AKT signaling pathway

Cited by 74 publications

References 21 publications

Critical Enzymatic Functions of FTO in Obesity and Cancer

Critical Enzymatic Functions of FTO in Obesity and Cancer

SKA3 promotes cell proliferation and migration in cervical cancer by activating the PI3K/Akt signaling pathway

Manganese‐12 acetate suppresses the migration, invasion, and epithelial–mesenchymal transition by inhibiting Wnt/β‐catenin and PI3K/AKT signaling pathways in breast cancer cells

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