Akt in cancer: Mediator and more

Revathidevi, Sundaramoorthy; Munirajan, Arasambattu Kannan

doi:10.1016/j.semcancer.2019.06.002

Cited by 489 publications

(345 citation statements)

References 173 publications

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“…AKT1 is widely expressed in many tissues, AKT2 is expressed in mainly insulin-sensitive tissues and at low levels in other tissues, and AKT3 is expressed in only the brain and testis. The specific tissue expression patterns of the different AKT subtypes suggest their key roles in the maintenance of physiological functions in different tissues or organs [22,23].…”

Section: Aktmentioning

confidence: 99%

RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours

et al. 2020

Cell Biosci

456

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: Aktmentioning

confidence: 99%

RETRACTED ARTICLE: Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours

et al. 2020

Cell Biosci

456

263

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“…Structure of Akts' amino terminus pleckstrin homology (PH) domain and central kinase domain is conserved across evolution, while the carboxyl terminus hydrophobic and proline-rich domain is more variable. The kinase activity of Akt is regulated by phosphorylation of Thr 308 and Ser 473 situated in the PH domain, although phosphorylation of Ser 124 and Thr 450 sites are needed for sensitizing Akt toward regulatory stimuli [13]. In the classical activation pathway of Akt (Figure 1), the upstream element PI3K phosphorylates phosphatidylinositol-4,5-bisphosphate to phosphatidylinositol-3,4,5-trisphosphate (PIP3) that binds to PH domain of the constitutively active 3-phosphoinositide-dependent protein kinase (PDK)1.…”

Section: Cellular Role and Regulation Of Aktmentioning

confidence: 99%

“…PIK3CA encodes the p110α catalytic subunit of PI3K, and is the most frequently altered oncogene in human cancers, including endometrial, ovarian, colorectal, and breast cancers [123]. Mutations of mTOR and Akt are much less frequent, although, they were demonstrated in melanoma, renal carcinoma, bladder tumor, lung cancer, breast cancers, head and neck squamous cell carcinomas, and endometrial cancer [124]. PTEN loss represent the second most mutated tumor suppressor gene frequently occurring in various human cancers including colorectal cancer, breast cancer, glioblastoma, endometrial cancer, malignant melanoma, and prostate cancer [125].…”

Section: Parp-akt Interactions In Cancer Biologymentioning

confidence: 99%

“…Although inhibitors of the pathway are attractive agents in the cancer therapy, so far no Akt inhibitor has been approved by FDA. On the other hand, FDA approved four PI3K and three mTOR inhibitors (Table 1) for clinical cancer therapy, and two Akt inhibitors are in phase III clinical trials for combination therapy of breast and colorectal cancers [124].…”

Section: Parp-akt Interactions In Cancer Biologymentioning

confidence: 99%

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Role of Akt Activation in PARP Inhibitor Resistance in Cancer

Gallyas

Sümegi

Szabó

2020

Cancers

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Poly(ADP-ribose) polymerase (PARP) inhibitors have recently been introduced in the therapy of several types of cancers not responding to conventional treatments. However, de novo and acquired PARP inhibitor resistance is a significant limiting factor in the clinical therapy, and the underlying mechanisms are not fully understood. Activity of the cytoprotective phosphatidylinositol-3 kinase (PI3K)-Akt pathway is often increased in human cancer that could result from mutation, expressional change, or amplification of upstream growth-related factor signaling elements or elements of the Akt pathway itself. However, PARP-inhibitor-induced activation of the cytoprotective PI3K-Akt pathway is overlooked, although it likely contributes to the development of PARP inhibitor resistance. Here, we briefly summarize the biological role of the PI3K-Akt pathway. Next, we overview the significance of the PARP-Akt interplay in shock, inflammation, cardiac and cerebral reperfusion, and cancer. We also discuss a recently discovered molecular mechanism that explains how PARP inhibition induces Akt activation and may account for apoptosis resistance and mitochondrial protection in oxidative stress and in cancer.

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“…The phosphatidylinositol-3 kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling network is frequently activated in an aberrant manner in most of human cancers, where it controls many processes essential for tumor growth and survival [7][8][9]. A large array of small molecule inhibitors of the PI3K/Akt/mTOR signaling pathway have been studied in preclinical models of human cancer, where their proved their efficacy as antineoplastic agents.…”

Section: Introductionmentioning

confidence: 99%