mTOR pathway: A current, up-to-date mini-review (Review)

Zarogoulidis, Paul; Lampaki, Sofia; Turner, J. Francis; Huang, Haidong; Kakolyris, Stylianos; Syrigos, Konstantinos; Zarogoulidis, Konstantinos

doi:10.3892/ol.2014.2608

Cited by 96 publications

(87 citation statements)

References 54 publications

(43 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The complex mTOR2 is composed of five sub-units: mTOR, mLST8, Rictor (large protein with molecular weight of 200 kDa), SIN1 (has several isoforms with molecular weights ranging from 52 to 80 kDa), and PROTOR, which is insensitive to the drug rapamycin [73]. Receptor tyrosine kinases (RTKs) are cell surface receptors for many polypeptide growth factors, cytokines, and hormones, including insulin.…”

Section: The Mtorc2 Pathway and Its Connection With The Mtorc1 Pathwamentioning

confidence: 99%

The Heat Shock Protein Story—From Taking mTORC1,2 and Heat Shock Protein Inhibitors as Therapeutic Measures for Treating Cancers to Development of Cancer Vaccines

Fung¹,

Kong²

2017

JCT

View full text Add to dashboard Cite

Heat shock proteins (HSPs) serve to correct proteins' conformation, send the damaged proteins for degradation (quality control function). Heat shock factors (HSFs) are their transcription factors. The protein complexes mTOR1 and 2 (with the same core mTOR), the phosphoinositide-dependent protein kinase-1 (PDK1), the seine/threonine-specific protein kinase (Akt), HSF1, plus their associated proteins form a network participating in protein synthesis, bio-energy generation, signaling for apoptosis with the help of HSPs. A cancer cell synthesizes proteins at fast rate and needs more HSPs to work on quality control. Shutting down this network would lead to cell death. Thus inhibitors of mTOR (mTORI) and inhibitors of HSPs (HSPI) could drive cancer cell to apoptosis-a "passive approach". On the other hand, HSPs form complexes with polypeptides characteristic of the cancer cells; on excretion from the cell, they becomes antigens for the immunity cells, eventually leading to maturation of the cytotoxic T cells, forming the basic principle of preparing cancer-specific, person-specific vaccine. Recent finding shows that HSP70 can penetrate cancer cell and expel its analog to extracellular region, giving the hope to prepare a non-person-specific vaccine covering a variety of cancers. Activation of anti-cancer immunity is the "active approach". On the other hand, mild hyperthermia, with increase of intracellular HSPs, has been found to activate the immunity response, and demonstrate anti-cancer effects. There are certain "mysteries" behind the mechanisms of the active and passive approaches. We analyze the mechanisms involved and provide explanations to some mysteries. We also suggest future research to improve our understanding of these two approaches, in which HSPs play many roles.

show abstract

Section: The Mtorc2 Pathway and Its Connection With The Mtorc1 Pathwamentioning

confidence: 99%

The Heat Shock Protein Story—From Taking mTORC1,2 and Heat Shock Protein Inhibitors as Therapeutic Measures for Treating Cancers to Development of Cancer Vaccines

Fung¹,

Kong²

2017

JCT

View full text Add to dashboard Cite

show abstract

“…Mammalian target of rapamycin (mTOR), a serine-threonine kinase that is highly conserved, is a component of the pathway cell survival phosphatidylinositol 3-kinase (PI3K) that monitors the availability of nutrients, mitogenic signals, cellular energy, and oxygen levels and is therefore insignificant in the regulation of cell growth and proliferation [11, 47, 48]. mTOR is regulated by nutrients and growth factor and regulates cell growth by controlling many biological process such as autophagia, mRNA translation, and energetic metabolism [Guertin and Sabatini, 2007] [49].…”

Section: M1 and M2 Differentiation And The Role Of Mtor Pathwaymentioning

confidence: 99%

“…The mTOR acts both upstream and downstream of the Akt, operating as a connection with PI3K pathway and forming two different multiprotein complexes, mTORC1 (mTOR complex 1) and mTORC2 (mTOR complex 2), which regulate protein synthesis required for cell growth and proliferation [48, 50]. The stimulation of TLRs by PAMPs leads to the recruitment of PI3K that activates mTORC1 and mTORC2 in macrophages [47].…”

Section: M1 and M2 Differentiation And The Role Of Mtor Pathwaymentioning

confidence: 99%

“…The mTORC1 may be inhibited physiologically by the action of TSC1 (tuberous sclerosis complex 1) and TSC2 (tuberous sclerosis complex 2) and by rapamycin due to the presence of Raptor (regulatory associated protein of mTOR) that is sensitive to the action of rapamycin [48, 50–53]. Mutations in TSC1 or TSC2 genes lead to tuberous sclerosis syndrome with the appearance of various benign tumors in skin, kidney, brain, heart, and lung [48, 50, 54].…”

Section: M1 and M2 Differentiation And The Role Of Mtor Pathwaymentioning

confidence: 99%

See 1 more Smart Citation

The Fate of the Tumor in the Hands of Microenvironment: Role of TAMs and mTOR Pathway

Soave

Miguel

Tomé

et al. 2016

Mediators of Inflammation

View full text Add to dashboard Cite

Since 2000, written with elegance and accuracy, Hanahan and Weinberg have proposed six major hallmarks of cancer and, together, they provide great advances to the understanding of tumoral biology. Our knowledge about tumor behavior has improved and the investigators have now recognized that inflammatory microenvironment may be a new feature for the tumor entities. Macrophages are considered as an important component of tumoral microenvironment. Biologically, two forms of activated macrophages can be observed: classically activated macrophages (M1) and alternative activated macrophages (M2). Despite the canonical pathways that control this puzzle of macrophages polarization, recently, mTOR signaling pathway has been implicated as an important piece in determining the metabolic and functional differentiation of M1 and M2 profiles. Currently, it is believed that macrophages related to tumoral microenvironment present an “M2-like” feature promoting an immunosuppressive microenvironment enhancing tumoral angiogenesis, growth, and metastasis. In the present review we discuss the role of macrophages in the tumor microenvironment and the role of mTOR pathway in M1 and M2 differentiation. We also discuss the recent findings in M1 and M2 polarization as a possible target in the cancer therapy.

show abstract

“…The mammalian target of rapamycin (mTOR) is a protein kinase that regulates cell survival and proliferation [77]. Due to its diverse functions, mTOR is implicated in many cancers making it an atractive target in treating tumors, including osteosarcoma.…”

Section: Mammalian Target Of Rapamycin (Mtor)mentioning

confidence: 99%

Osteosarcomagenesis: Biology, Development, Metastasis, and Mechanisms of Pain

Smeester¹,

Moriarity²,

Beitz³

2017

Osteosarcoma - Biology, Behavior and Mechanisms

View full text Add to dashboard Cite

Osteosarcoma is the most common primary cancer of the bone and third most common cancer in children and adolescents with approximately 900 new cases annually in the United States. A major facet of osteosarcoma is its high level of genomic instability, in particular chromosomal instability, which is the result of increased or decreased chromosome number in a cell. Furthermore, pain is the most common symptomatic feature of osteosarcoma that lacks efective therapy. Pain in osteosarcoma is relatively more complicated than many other painful conditions requiring a more thorough understanding of its etiology, pathobiology, and neurobiology to allow the development of beter therapies for reducing pain in osteosarcoma patients. Studies are underway to deine the diverse modalities of presentation, growth, development, metastases, and nociception in osteosarcoma. New data from human studies in combination with data from studies incorporating transgenic mouse models of osteosarcoma are providing valuable insights into the mechanisms underlying the development of both the tumor and the tumor-induced pain. These new data will undoubtedly lead to improved prognoses, as well as the development of novel therapeutics that will signiicantly decrease bone cancer pain.

show abstract

mTOR pathway: A current, up-to-date mini-review (Review)

Cited by 96 publications

References 54 publications

The Heat Shock Protein Story—From Taking mTORC1,2 and Heat Shock Protein Inhibitors as Therapeutic Measures for Treating Cancers to Development of Cancer Vaccines

The Heat Shock Protein Story—From Taking mTORC1,2 and Heat Shock Protein Inhibitors as Therapeutic Measures for Treating Cancers to Development of Cancer Vaccines

The Fate of the Tumor in the Hands of Microenvironment: Role of TAMs and mTOR Pathway

Osteosarcomagenesis: Biology, Development, Metastasis, and Mechanisms of Pain

Contact Info

Product

Resources

About