All Roads Lead to mTOR: Integrating Inflammation and Tumor Angiogenesis
Open accessAbstract
Mammalian target of rapamycin (mTOR) is a crucial molecule in the control of cell size and proliferation; dysregulation of the mTOR pathway is commonly found in human cancers. Many cancer-promoting kinases have been identified as regulators of mTOR activity through phosphorylation and inactivation of the TSC1-TSC2 complex. Tumorassociated macrophages (TAMs) are tumor-promoting factors in inflammation-mediated tumor development, and the signaling molecules involved in TAMs-mediated tumor angiogenesis are not well understood. Therefore, it is urgent to elucidate the cross-talk between inflammatory cells and cancers and to explore the precise pathways involved in TAMsinduced tumor angiogenesis. Recently IKKbeta was found to activate the mTOR pathway and to promote tumor angiogenesis through inactivation of the TSC1-TSC2 complex by phosphorylating TSC1. This finding provides critical insights into and suggests one mechanism behind inflammation-mediated tumor angiogenesis. In this extra-view, we briefly discuss the possible influence of TAMs-released proangiogenic factors on mTOR activation and propose a model of the cross-talk between tumors and TAMs in tumor angiogenesis.
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This provides a strong link between pro-inflammatory immune factors, body growth through activation of the mTOR pathway and uncontrolled proliferation typical of cancer-related disease.
“This provides a strong link between pro-inflammatory immune factors, body growth through activation of the mTOR pathway and uncontrolled proliferation typical of cancer-related disease [150, 151–153].”
From The ASD Living Biology: from cell proliferation to clinical phenotype (2019) · cites this paper as [151]
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BackgroundThe Concept of Hormesis in Cancer Therapy – Is Less More?
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“As such, it integrates a wide range of growth factors and hormonal signals and is a key regulator of cell growth and proliferation [57-58].”
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“It has been shown that inflammation-related factors can activate MTOR can promote tumor angiogenesis by phosphorylating TSC1 (also known as hamartin) and thereby inactivating the TSC1-TSC2 complex [22, 23].”
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“Following ERK1/2 activation, mTOR has been shown to be regulated via the tuberous sclerosis complex 1 and 2 (TSC1/2 also called Hamartin and Tuberin) [33,34].”
MethodSirolimus Therapy as Perioperative Treatment of Gorham-Stout Disease in the Thoracic Spine
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Overgrowth Syndromes Associated With Vascular Anomalies
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Temsirolimus targets multiple hallmarks of cancer to impede mesothelioma growth in vivo
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“Activation of the AKT/mTOR pathway has been associated with aggressive disease and poor prognosis in certain cancers, like breast cancer [29-33].”
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“Beyond metabolic adaptation and cell survival regulation, biological adaptive programs modulate other cellular functions, including immunity [4, 5].”
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“The plausibility of this assumption is supported by the ability of NF-kB signaling to impact mTOR activation, as well as the well-established role of LPS as a potent inducer of IKKs and subsequent inflammatory responses [26, 27].”
BackgroundOptimization of Initial Dose Regimen for Sirolimus in Pediatric Patients With Lymphangioma
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“Sirolimus can block the mTOR signaling and further inhibit abnormal vascular proliferation, reducing the production of vascular endothelial growth factor and responsiveness of its receptors (Neuhaus et al., 2001; Huber et al., 2007; Kobayashi et al., 2007; Lee and Hung, 2007; Hammill et al., 2011; Shibuya, 2011).”
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“For instance, Lee and Hung (55) found that mTOR links the inflammatory response to tumor angiogenesis via IKK-b (a NF-KB activator).”
BackgroundThe use of rapamycin to treat vascular tumours and malformations: A single-centre experience
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“, PI3K, AKT), and its activation has been associated with angiogenesis and lymphangiogenesis (9,10).”
BackgroundEffects of the MTOR and AKT1 genes polymorphisms on papillary thyroid cancer development
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“MTORC1 and mTORC2 are two multiprotein complexes of mTOR, involved in the cell proliferation and growth.(7) The PI3K/AKt and mTOR pathways regulate many parts of cell survival and growth, both in the physiological and pathological conditions.”
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Cellular Mechanisms and Therapeutic Targeting of Long Noncoding RNAs in Atherosclerotic Disease
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“…activation of mTOR has been associated with enhanced VSMCs proliferation and migration, contributing to neointima formation and plaque development [96]. mTOR signaling also supports inflammatory cytokine production and matrix re-modeling by promoting the expression of interleukins and MMPs [97].”
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“Enhanced mTOR signaling increases expression of the vascular endothelial growth factor, which is a master switch in angiogenesis and lymphangiogenesis [9].”
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“Studies have found that both TNF-α and IL-6 can induce the activation of mTORC1.(30,31) Thus, the increased expression of TNF-α and IL-6 could lead to higher LDLr expression in the subconjunctival fibroblasts and subconjunctival tissues from the RG group than the other two groups.”
BackgroundAre We Hitting the Right Combination for Hormonally Sensitive Breast Cancer?
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Microcystic lymphatic malformation presenting as firm, skin‐colored papules of the lips
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“Surgical excision may be employed as a primary treatment or alongside other nonsurgical modalities such as radiofrequency ablation, laser, bleomycin sclerotherapy,(4) and the use of oral or topical sirolimus, which targets the mTOR/phosphoinositide-3-kinase (PI3K) pathway.(5)”
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“[69] Lee, D.”
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“surrounding this mechanism, recent studies indicate that the temporal sequence of TNFa activation is important to the in vivo angiogenic response and that this involves an intracellular signalling pathway involving JNK, nuclear factor jB (NFjB) and IjB kinase (IKK) [30–34].”
Background
- Authors
- Lee, D.-F., & Hung, M.-C.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2007-12-15
- Volume
- 6
- Issue
- 24
- Pages
- 3011-3014
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- OpenAlex
- W2015793629
- Cited by
- 115
- References
- 0
- Citations by year
- 2026: 4 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 8 · 2020: 6 · 2019: 13 · 2018: 8 · 2017: 5 · 2016: 3 · 2015: 13 · 2014: 10 · 2013: 4 · 2012: 7
- FWCI
- 0.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Cycle (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Breast Cancer Research Foundation (W81XWH-05-1-0252, CA16672)
- National Institutes of Health (CA-16 672, W81XWH, CA116199, CA099031)
- National Cancer Institute (P50CA116199, CA-16672, R01CA109311, Ca-116199, P01CA099031, P30CA016672)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- mTOR signaling, tumor angiogenesis, tumor-associated macrophages, inflammation, TSC1/TSC2 complex, IKKβ, angiogenic factors, cancer
- MeSH terms
- Tuberous Sclerosis Complex 1 Protein, Tuberous Sclerosis Complex 2 Protein, Animals, Humans, Neoplasms, Neovascularization, Pathologic, Phosphorylation, Protein Kinases, Signal Transduction, Tumor Suppressor Proteins, I-kappa B Kinase, TOR Serine-Threonine Kinases
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