Role of AKT and mTOR signaling pathways in the induction of epithelial-mesenchymal transition (EMT) process

Roshan, Mostafa Karimi; Soltani, Arash; Soleimani, Anvar; Kahkhaie, Kolsoum Rezaie; Afshari, Amir R.; Soukhtanloo, Mohammad

doi:10.1016/j.biochi.2019.08.003

Cited by 175 publications

(113 citation statements)

References 68 publications

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“…Following phosphorylation of TSC2 by AKT, TSC2 loses its ability to inhibit mTORC1 and activate mTOR. In addition, TSC2 can be directly activated by AMPK phosphorylation, and AKT can completely inhibit TSC2 and activate mTOR by inhibiting AMPK [59,60].…”

Section: Akt Target Proteinsmentioning

confidence: 99%

RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours

et al. 2020

Cell Biosci

469

263

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The PI3 K/AKT/mTOR signalling pathway plays an important role in the regulation of signal transduction and biological processes such as cell proliferation, apoptosis, metabolism and angiogenesis. Compared with those of other signalling pathways, the components of the PI3K/AKT/mTOR signalling pathway are complicated. The regulatory mechanisms and biological functions of the PI3K/AKT/mTOR signalling pathway are important in many human diseases, including ischaemic brain injury, neurodegenerative diseases, and tumours. PI3K/AKT/mTOR signalling pathway inhibitors include single-component and dual inhibitors. Numerous PI3K inhibitors have exhibited good results in preclinical studies, and some have been clinically tested in haematologic malignancies and solid tumours. In this review, we briefly summarize the results of research on the PI3K/AKT/mTOR pathway and discuss the structural composition, activation, communication processes, regulatory mechanisms and biological functions of the PI3K/AKT/mTOR signalling pathway in the pathogenesis of neurodegenerative diseases and tumours.

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Section: Akt Target Proteinsmentioning

confidence: 99%

RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours

et al. 2020

Cell Biosci

469

263

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“…Recent studies have emphasized the role of the AKT signaling pathway in the induction of EMT in different cancer cells [31]. AKT, a Serine/Threonine kinase, is a key component in numerous processes, can phosphorylate and then regulate vital downstream effector molecules, including FOXO, mTOR, GSK3b, and promote cancer cell growth, metabolism and survival and induce EMT and metastasis [32]. Phosphorylation of AKT is a key step in the activation of AKT pathway.…”

Section: Discussionmentioning

confidence: 99%

FABP4 promotes invasion and metastasis of colon cancer by regulating fatty acid transport

Tian

Zhang

et al. 2020

Cancer Cell Int

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Background The prognosis of colon cancer is poor for metastasis, while the mechanism, especially adipocytes related, is not yet clear. The purpose of this study is to determine the effects of fatty acid binding protein 4 (FABP4), a transporter for lipids, on colon cancer progression. Methods The distribution of lipids and FABP4 was tested in the colon cancer tissues and adjacent normal tissues, and their relationship was also verified in vitro. Experiments about cellular invasion, migration and proliferation were performed to detect the impacts of FABP4 on the biological behaviors of colon cancer, and the positive results were checked in vivo. Meanwhile, the regulatory role of FABP4 in the energy and lipid metabolism was evaluated by the levels of triglyceride, ATP, LDH, glycerol and NEFA. At last, GO and KEGG analysis based on FABP4 overexpressed cells was performed, and the AKT pathway and epithelial–mesenchymal transition (EMT)-related proteins were determined by Western blot. Results Higher accumulation of lipids and stronger FABP4 transcription were observed in colon cancer tissues. Having been incubated with adipose tissue extract and overexpressed FABP4, colon cancer cells demonstrated enhanced lipid accumulation. In functional experiments, co-culture with adipose tissue extract significantly enhanced the invasion and migration of colon cancer cells, as well as the energy and lipid metabolism, and all these processes were reversed by FABP4 inhibitor. In addition, the metastasis of FABP4-overexpressed colon cancer cells was also significantly enhanced in vitro and in vivo. In terms of mechanism, the bioinformatics analysis showed that FABP4 was enriched in 11 pathways related to metabolic processes in FABP4 overexpressed cells. Finally, FABP4 overexpression improved EMT progression of colon cancer, as evidenced by the upregulation of Snail, MMP-2 and MMP-9, the downregulation of E-cadherin. The expression of p-Akt was also elevated. Conclusion FABP4 overexpression could increase FAs transport to enhance energy and lipid metabolism, and activate AKT pathway and EMT to promote the migration and invasion of colon cancer cells.

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“…PI3K/AKT/mTOR signaling pathway controls cell growth, proliferation, cell polarity and cytoskeleton, and EMT and angiogenesis (Peng et al, 2014;Arash and Amirhossein, 2017;Falguni et al, 2018). Recent studies have shown that activated PI3K/AKT/mTOR signaling pathway can induce EMT process, especially E-cadherin level and inhibit matrix metalloproteinases (MMPs) (Karimi et al, 2019). MMPs can degrade almost all ECM components and E-cadherin, except polysaccharide (Oskar et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Deciphering the Pharmacological Mechanisms of Taohe-Chengqi Decoction Extract Against Renal Fibrosis Through Integrating Network Pharmacology and Experimental Validation In Vitro and In Vivo

Zhou

et al. 2020

Front. Pharmacol.

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Role of AKT and mTOR signaling pathways in the induction of epithelial-mesenchymal transition (EMT) process

Cited by 175 publications

References 68 publications

RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours

RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours

FABP4 promotes invasion and metastasis of colon cancer by regulating fatty acid transport

Deciphering the Pharmacological Mechanisms of Taohe-Chengqi Decoction Extract Against Renal Fibrosis Through Integrating Network Pharmacology and Experimental Validation In Vitro and In Vivo

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