Positive feedback regulation between Akt phosphorylation and fatty acid synthase expression in osteosarcoma

Wang, Heng; Luo, Qing; Peng, Ai; Long, Xin; Wang, Tao Fang; Liu, Zhi Li; Zhang, Guo Mei; Zhou, Rong; Gao, Song; Zhou, Yang; Chen, Wen Zhao

doi:10.3892/ijmm.2013.1602

Cited by 22 publications

(20 citation statements)

References 34 publications

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“…Furthermore, the association between FASN downregulation and PI3K signaling, which is already documented (54–57) , could be confirmed by our data from respective genome-wide expression analyses ( Figure 4 ), which included the FASN inhibitor C75 as a control, thus emphasizing this pathway as a potential target for anticancer therapy (58) .…”

Section: Resultssupporting

confidence: 80%

Inhibition of the mevalonate pathway affects epigenetic regulation in cancer cells

et al. 2015

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The mevalonate pathway provides metabolites for post-translational modifications such as farnesylation, which are critical for the activity of RAS downstream signaling. Subsequently occurring regulatory processes can induce an aberrant stimulation of DNA methyltransferase (DNMT1) as well as changes in histone deacetylases (HDACs) and microRNAs in many cancer cell lines. Inhibitors of the mevalonate pathway are increasingly recognized as anticancer drugs. Extensive evidence indicates an intense cross-talk between signaling pathways, which affect growth, differentiation, and apoptosis either directly or indirectly via epigenetic mechanisms. Herein, we show data obtained by novel transcriptomic and corresponding methylomic or proteomic analyses from cell lines treated with pharmacologic doses of respective inhibitors (i.e., simvastatin, ibandronate). Metabolic pathways and their epigenetic consequences appear to be affected by a changed concentration of NADPH. Moreover, since the mevalonate metabolism is part of a signaling network, including vitamin D metabolism or fatty acid synthesis, the epigenetic activity of associated pathways is also presented. This emphasizes the far-reaching epigenetic impact of metabolic therapies on cancer cells and provides some explanation for clinical observations, which indicate the anticancer activity of statins and bisphosphonates.

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Section: Resultssupporting

confidence: 80%

Inhibition of the mevalonate pathway affects epigenetic regulation in cancer cells

et al. 2015

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“…Previous studies have shown that alteration of the PI3K/AKT pathway is strongly implicated in OS pathogenesis. Moreover, studies have suggested that inhibition of the PI3K/AKT pathway disrupts functions essential for OS progression (36,37). Graziano et al (38) found that Wilms' tumor gene 1 (WT1) silencing inhibits OS cell proliferation by downregulating PI3K/AKT pathway.…”

Section: Discussionmentioning

confidence: 99%

TROP2 promotes cell proliferation and migration in osteosarcoma through PI3K/AKT signaling

Nijiati

Gao

et al. 2018

Mol Med Report

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Human trophoblast cell surface antigen 2 (TROP2) has been noted to serve an important role in the proliferation and migration of various types of human cancers. However, the potential role and the molecular mechanisms of TROP2 in osteosarcoma (OS) remain largely unclear. In the present study, high expression of TROP2 in human OS tissues and cell lines was observed. Overexpression of TROP2 promoted the proliferation and migration of OS cell lines, while TROP2 knockdown markedly decreased cell growth and migration. Furthermore, it was revealed that TROP2 overexpression significantly activated the phosphoinositide 3‑kinase/protein kinase B (PI3K/AKT) signaling pathway. Collectively, these results suggested that TROP2 may promote OS cell proliferation and migration via PI3K/AKT signaling and may serve as a novel treatment target for OS.

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“…FASN modulates receptor localisation through palmitoylation and promotes the activation of oncogenic signalling pathways, such as the Akt/mTOR signalling pathway (5). The Akt/mTOR signalling pathway also promotes the transcription of FASN, thereby forming a positive feedback regulation (45,46). The downregulation of FASN inhibited cancer cell invasion and migration by targeting the Akt/mTOR signalling pathway (47)(48)(49).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-1207-5p inhibits hepatocellular carcinoma cell growth and invasion through the fatty acid synthase-mediated Akt/mTOR signalling pathway

et al. 2016

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Fatty acid synthase (FASN) has emerged as a unique oncologic target for the treatment of cancers, including hepatocellular carcinoma (HCC). However, effective inhibitors of FASN for cancer treatment are lacking. MicroRNAs (miRNAs) have emerged as novel and endogenic inhibitors of gene expression. In the present study, we aimed to investigate the role of miR‑1207‑5p in HCC and the regulation of FASN through miR‑1207‑5p. The expression of miR-1207-5p was markedly reduced in HCC tissues and cell lines as detected with real‑time quantitative polymerase chain reaction (qPCR). Overexpression of miR-1207-5p significantly suppressed the cell growth and invasion of HCC cells. By contrast, inhibition of miR‑1207‑5p exhibited an opposite effect. Bioinformatics analysis showed that FASN is a predicted target of miR‑1207‑5p which was validated by dual‑luciferase reporter assay, qPCR and western blot analysis. Overexpression of miR‑1207‑5p inhibited the Akt/mTOR signalling pathway, and promotion of this pathway was noted following inhibition of miR‑1207‑5p. Rescue experiments showed that the restoration of FASN expression partially reversed the inhibitory effect of miR‑1207‑5p on cell growth, invasion and Akt phosphorylation. In conclusion, our study suggests that miR‑1207‑5p/FASN plays an important role in HCC, and provides novel insight into developing new inhibitors for FASN for therapeutic interventions for HCC.

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Positive feedback regulation between Akt phosphorylation and fatty acid synthase expression in osteosarcoma

Cited by 22 publications

References 34 publications

Inhibition of the mevalonate pathway affects epigenetic regulation in cancer cells

Inhibition of the mevalonate pathway affects epigenetic regulation in cancer cells

TROP2 promotes cell proliferation and migration in osteosarcoma through PI3K/AKT signaling

MicroRNA-1207-5p inhibits hepatocellular carcinoma cell growth and invasion through the fatty acid synthase-mediated Akt/mTOR signalling pathway

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