The Esophageal Cancer and the PI3K/AKT/mTOR Signaling Regulatory microRNAs: a Novel Marker for Prognosis, and a Possible Target for Immunotherapy

2019 ◽  
Vol 24 (39) ◽  
pp. 4646-4651 ◽  
Author(s):  
Seyed A. Javadinia ◽  
Soodabeh Shahidsales ◽  
Azar Fanipakdel ◽  
Asma Mostafapour ◽  
Mona Joudi-Mashhad ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cross Talk ◽  
Therapeutic Target ◽  
Cell Biology ◽  
Current Knowledge ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Pathway ◽  
Mtor Signaling ◽  
Phosphatidylinositol 3 Kinase ◽  
Potential Therapeutic Target

The Phosphatidylinositol 3-kinase/AKT/Mammalian Target of Rapamycin (PI3K/AKT/mTOR) pathway has a critical regulatory role in cell biology including translation, transcription, and autophagy. Dysregulation of this pathway is involved in the pathogenesis, development, and prognosis of esophageal cancer that has been assessed in the recent years and its potential as a target in therapy. This report summarizes the current knowledge about PI3K/AKT/mTOR pathway and its cross-talk with a focus on the value of targeting this pathway as a potential therapeutic target in the treatment of esophageal cancer.

Targeting mammalian target of rapamycin: prospects for the treatment of inflammatory bowel diseases

2020 ◽  
Vol 27 ◽  
Author(s):  
Naser-Aldin Lashgari ◽  
Nazanin Momeni Roudsari ◽  
Saeideh Momtaz ◽  
Negar Ghanaatian ◽  
Parichehr Kohansal ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Pathway ◽  
Mtor Signaling ◽  
Target Of Rapamycin ◽  
In Vivo Studies ◽  
Cochrane Library ◽  
Mtor Signaling Pathway ◽  
Inflammatory Bowel

: Inflammatory bowel disease (IBD) is a general term for a group of chronic and progressive disorders. Several cellular and biomolecular pathways are implicated in the pathogenesis of IBD, yet the etiology is unclear. Activation of the mammalian target of rapamycin (mTOR) pathway in the intestinal epithelial cells was also shown to induce inflammation. This review focuses on the inhibition of the mTOR signaling pathway and its potential application in treating IBD. We also provide an overview on plant-derived compounds that are beneficial for the IBD management through modulation of the mTOR pathway. Data were extracted from clinical, in vitro and in vivo studies published in English between 1995 and May 2019, which were collected from PubMed, Google Scholar, Scopus and Cochrane library databases. Results of various studies implied that inhibition of the mTOR signaling pathway downregulates the inflammatory processes and cytokines involved in IBD. In this context, a number of natural products might reverse the pathological features of the disease. Furthermore, mTOR provides a novel drug target for IBD. Comprehensive clinical studies are required to confirm the efficacy of mTOR inhibitors in treating IBD.

scholarly journals mTOR Signaling at the Crossroad between Metazoan Regeneration and Human Diseases

2020 ◽  
Vol 21 (8) ◽  
pp. 2718 ◽  
Author(s):  
Yasmine Lund-Ricard ◽  
Patrick Cormier ◽  
Julia Morales ◽  
Agnès Boutet
Keyword(s):  
Evolutionary Biology ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Pathway ◽  
Mtor Signaling ◽  
Human Diseases ◽  
Whole Body ◽  
Body Parts ◽  
Animal Kingdom ◽  
Structure Damage ◽  
Wide Range

A major challenge in medical research resides in controlling the molecular processes of tissue regeneration, as organ and structure damage are central to several human diseases. A survey of the literature reveals that mTOR (mechanistic/mammalian target of rapamycin) is involved in a wide range of regeneration mechanisms in the animal kingdom. More particularly, cellular processes such as growth, proliferation, and differentiation are controlled by mTOR. In addition, autophagy, stem cell maintenance or the newly described intermediate quiescence state, Galert, imply upstream monitoring by the mTOR pathway. In this review, we report the role of mTOR signaling in reparative regenerations in different tissues and body parts (e.g., axon, skeletal muscle, liver, epithelia, appendages, kidney, and whole-body), and highlight how the mTOR kinase can be viewed as a therapeutic target to boost organ repair. Studies in this area have focused on modulating the mTOR pathway in various animal models to elucidate its contribution to regeneration. The diversity of metazoan species used to identify the implication of this pathway might then serve applied medicine (in better understanding what is required for efficient treatments in human diseases) but also evolutionary biology. Indeed, species-specific differences in mTOR modulation can contain the keys to appreciate why certain regeneration processes have been lost or conserved in the animal kingdom.

scholarly journals Targeting AKT/mTOR in Oral Cancer: Mechanisms and Advances in Clinical Trials

2020 ◽  
Vol 21 (9) ◽  
pp. 3285 ◽  
Author(s):  
Choudhary Harsha ◽  
Kishore Banik ◽  
Hui Li Ang ◽  
Sosmitha Girisa ◽  
Rajesh Vikkurthi ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Inhibitors ◽  
Mtor Pathway ◽  
Mtor Signaling ◽  
Therapeutic Interventions ◽  
Treatment Modalities ◽  
Disease Heterogeneity ◽  
Mesenchymal Transition

Oral cancer (OC) is a devastating disease that takes the lives of lots of people globally every year. The current spectrum of treatment modalities does not meet the needs of the patients. The disease heterogeneity demands personalized medicine or targeted therapies. Therefore, there is an urgent need to identify potential targets for the treatment of OC. Abundant evidence has suggested that the components of the protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) pathway are intrinsic factors for carcinogenesis. The AKT protein is central to the proliferation and survival of normal and cancer cells, and its downstream protein, mTOR, also plays an indispensable role in the cellular processes. The wide involvement of the AKT/mTOR pathway has been noted in oral squamous cell carcinoma (OSCC). This axis significantly regulates the various hallmarks of cancer, like proliferation, survival, angiogenesis, invasion, metastasis, autophagy, and epithelial-to-mesenchymal transition (EMT). Activated AKT/mTOR signaling is also associated with circadian signaling, chemoresistance and radio-resistance in OC cells. Several miRNAs, circRNAs and lncRNAs also modulate this pathway. The association of this axis with the process of tumorigenesis has culminated in the identification of its specific inhibitors for the prevention and treatment of OC. In this review, we discussed the significance of AKT/mTOR signaling in OC and its potential as a therapeutic target for the management of OC. This article also provided an update on several AKT/mTOR inhibitors that emerged as promising candidates for therapeutic interventions against OC/head and neck cancer (HNC) in clinical studies.

The role of mTOR inhibitors in targeting a putative cancer stem cell-like population in esophageal cancer.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 43-43
Author(s):  
Da Wang ◽  
Roland Chiu ◽  
John Theodorus Plukker ◽  
Robert P. Coppes
Keyword(s):  
Esophageal Cancer ◽  
Cell Lines ◽  
Mammalian Target Of Rapamycin ◽  
Neoadjuvant Chemoradiotherapy ◽  
Mtor Inhibitors ◽  
Mtor Pathway ◽  
Tumor Biopsy ◽  
Sphere Formation ◽  
Dose Dependent

43 Background: Despite modern advances in the treatment of esophageal cancer (EC), using neoadjuvant chemoradiotherapy (CRT) and esophagectomy, most patients face poor outcome. Growing evidence indicates that cancer stem cells (CSCs) might contribute to the poor prospects. CSCs are usually resistant to CRT and ultimately can generate a new tumor. The mammalian target of rapamycin (mTOR) pathway is associated with cancer stemness. However, its role in EC CSC-like populations needs to be elucidated. Here, we investigate the role of mTOR pathway on the stemness of a putative CSC-like population. Methods: Previously, we identified a putative CSC-like population (CD44+/CD24-) in EC cell lines and in tumor biopsy from EC patients. qPCR was used to measure the expression of mTOR in CD44+/CD24- CSC-like population of OE21 squamous cell carcinoma and OE33 adenocarcinoma cell lines compared to controls, that consisted of solid tumors generated from the same cell lines obtained from xenografts. mTOR inhibitors rapamycin and torin-1 were used to see their effect on CD44+/CD24- expression and sphere formation. Results: mTOR expression was 2-fold up-regulated in the OE33 CD44+/CD24- CSC-like population compared to control. Furthermore, in OE21 this up-regulation was 1.9-fold. Surprisingly, inhibiting the mTOR pathway with rapamycin enhanced OE33 CD44+/CD24- expression compared to its control (p = 0.01). In pilot experiments this effect was dose dependent and cells treated with rapamycin formed more spheres than control. Rapamycin did not alter the expression of CD44+/CD24- in OE21. Inhibiting the mTOR pathway with Torin-1 enhanced OE21 CD44+/CD24- expression by 1.2-fold compared to control (N = 2). In another pilot experiment Torin-1 treated cells were able to form more spheres compared to control. Torin-1 did not have an effect on the expression of CD44+/CD24- in OE33. Conclusions: These findings indicate that inhibiting the mTOR pathway may enhance CSC-like properties in EC. Additional research needs to be done to further support this hypothesis and elucidate the mechanism in this process. Furthermore, the effect of mTOR pathway inducers in EC needs to be explored.

scholarly journals Emerging Role of mTOR Signaling-Related miRNAs in Cardiovascular Diseases

2018 ◽  
Vol 2018 ◽  
pp. 1-23 ◽  
Author(s):  
Arun Samidurai ◽  
Rakesh C. Kukreja ◽  
Anindita Das
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Signaling Pathway ◽  
Noncoding Rna ◽  
Current Knowledge ◽  
Mammalian Target Of Rapamycin ◽  
Vital Role ◽  
Mtor Signaling ◽  
Cellular Growth ◽  
Mtor Signaling Pathway

Mechanistic/mammalian target of rapamycin (mTOR), an atypical serine/threonine kinase of the phosphoinositide 3-kinase- (PI3K-) related kinase family, elicits a vital role in diverse cellular processes, including cellular growth, proliferation, survival, protein synthesis, autophagy, and metabolism. In the cardiovascular system, the mTOR signaling pathway integrates both intracellular and extracellular signals and serves as a central regulator of both physiological and pathological processes. MicroRNAs (miRs), a class of short noncoding RNA, are an emerging intricate posttranscriptional modulator of critical gene expression for the development and maintenance of homeostasis across a wide array of tissues, including the cardiovascular system. Over the last decade, numerous studies have revealed an interplay between miRNAs and the mTOR signaling circuit in the different cardiovascular pathophysiology, like myocardial infarction, hypertrophy, fibrosis, heart failure, arrhythmia, inflammation, and atherosclerosis. In this review, we provide a comprehensive state of the current knowledge regarding the mechanisms of interactions between the mTOR signaling pathway and miRs. We have also highlighted the latest advances on mTOR-targeted therapy in clinical trials and the new perspective therapeutic strategies with mTOR-targeting miRs in cardiovascular diseases.

Deletion of the amino acid transporter Slc6a14 suppresses tumour growth in spontaneous mouse models of breast cancer

2015 ◽  
Vol 469 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Ellappan Babu ◽  
Yangzom D. Bhutia ◽  
Sabarish Ramachandran ◽  
Jaya P. Gnanaprakasam ◽  
Puttur D. Prasad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Amino Acid ◽  
Mouse Models ◽  
Therapeutic Target ◽  
Tumour Growth ◽  
Mammalian Target Of Rapamycin ◽  
Amino Acid Transporter ◽  
Mtor Pathway ◽  
Target Of Rapamycin ◽  
Acid Transporter

Deletion of the amino acid transporter Slc6a14 in mice suppresses tumour growth in spontaneous models of breast cancer via interference with mammalian target of rapamycin (mTOR) pathway; this indicates an obligatory role for SLC6A14 in breast cancer, highlighting its potential as a therapeutic target.

PI(3)K–Akt–mTOR pathway as a potential therapeutic target in neuroendocrine tumors

2008 ◽  
Vol 3 (2) ◽  
pp. 207-222 ◽  
Author(s):  
Kathrin Zitzmann ◽  
George Vlotides ◽  
Burkhard Göke ◽  
Christoph J Auernhammer
Keyword(s):  
Neuroendocrine Tumors ◽  
Therapeutic Target ◽  
Mtor Pathway ◽  
Potential Therapeutic Target

scholarly journals Survivin Ser81 Plays An Important Role in PI3K/Akt/mTOR Signaling Pathway

2018 ◽  
Vol 2 (2) ◽  
pp. 55
Author(s):  
Ferry Sandra
Keyword(s):  
Viral Particle ◽  
Mammalian Target Of Rapamycin ◽  
Phosphorylation Site ◽  
Mtor Signaling ◽  
Dependent Manner ◽  
Phosphatidylinositol 3 Kinase ◽  
Concentration Dependent Manner ◽  
L929 Cells ◽  
Phosphorylated Akt ◽  
Apoptosis Protein

Background: Survivin, a member of the inhibitor of apoptosis protein family, has been associated with protection from cell apoptosis and regulation of mitosis. Phosphorylated-Survivin at Ser81 was reported to provide cytoprotection against tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in L929 cells by inducing a backloop activation of phosphatidylinositol 3-kinase (PI3K). Therefore Akt as a possible substrate of PI3K was investigated.Methods: L929 cells were pretreated with/without 50 μM LY294002 or 10 μM Perifosine, and infected with viral particle of Survivin, anti sense of Survivin, Ser81Ala mutated Survivin or vector only. Cells were then harvested, lysed and subjected to immunoblot assay to detect Akt, phosphorylated Akt (Ser473), mammalian target of rapamycin (mTOR), phosphorylated-mTOR (Ser2448).Results: Survivin induced Akt and mTOR phosphorylations in a viral particle concentration dependent manner. Pretreatment of LY294002 or Perifosine prior to Survivin infection, attenuated Akt or mTOR phosphorylations, respectively. Low Akt or mTOR phosphorylations were observed when L929 cells were infected with Ser81Ala mutated Survivin.Conclusion: Ser81 phosphorylation site of Survivin played an important role in activating Survivin/PKA/PI3K/Akt/mTOR signaling pathway.Keywords: survivin, Ser81, Akt, mTOR, LY294002, perifosine

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