mTOR signaling and its involvement in the regulation of cell movements through remodeling the cytoskeleton architecture

Kosach, V. R.; Cherednyk, O. V.; Хоруженко, А. И.

doi:10.7124/bc.0008c7

Cited by 3 publications

(3 citation statements)

References 48 publications

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“…The mTOR signaling pathway senses nutrient availability and can switch on autophagy during times of nutrient stress [ 40 ]. This pathway also integrates information about cellular nutrient and energy status with cytoskeletal dynamics, remodeling the actin cytoskeleton to facilitate invasion and metastasis [ 41 , 42 ]. Our data suggest that autophagy and the remodeling of cytoskeleton dynamics is playing a role in antifolate drug resistance.…”

Section: Discussionmentioning

confidence: 99%

Unlocking the Molecular Secrets of Antifolate Drug Resistance: A Multi-Omics Investigation of the NCI-60 Cell Line Panel

Rushing

2023

Biomedicines

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Drug resistance continues to be a significant problem in cancer therapy, leading to relapse and associated mortality. Although substantial progress has been made in understanding drug resistance, significant knowledge gaps remain concerning the molecular underpinnings that drive drug resistance and which processes are unique to certain drug classes. The NCI-60 cell line panel program has evaluated the activity of numerous anticancer agents against many common cancer cell line models and represents a highly valuable resource to study intrinsic drug resistance. Furthermore, great efforts have been undertaken to collect high-quality omics datasets to characterize these cell lines. The current study takes these two sources of data—drug response and omics profiles—and uses a multi-omics investigation to uncover molecular networks that differentiate cancer cells that are sensitive or resistant to antifolates, which is a commonly used class of anticancer drugs. Results from a combination of univariate and multivariate analyses showed numerous metabolic processes that differentiate sensitive and resistant cells, including differences in glycolysis and gluconeogenesis, arginine and proline metabolism, beta-alanine metabolism, purine metabolism, and pyrimidine metabolism. Further analysis using multivariate and integrated pathway analysis indicated purine metabolism as the major metabolic process separating cancer cells sensitive or resistant to antifolates. Additional pathways differentiating sensitive and resistant cells included autophagy-related processes (e.g., phagosome, lysosome, autophagy, mitophagy) and adhesion/cytoskeleton-related pathways (e.g., focal adhesion, regulation of actin cytoskeleton, tight junction). Volcano plot analysis and the receiver operating characteristic (ROC) curves of top selected variables differentiating Q1 and Q4 revealed the importance of genes involved in the regulation of the cytoskeleton and extracellular matrix (ECM). These results provide novel insights toward mechanisms of intrinsic antifolate resistance as it relates to interactions between nucleotide metabolism, autophagy, and the cytoskeleton. These processes should be evaluated in future studies to potentially derive novel therapeutic strategies and personalized treatment approaches to improve antifolate response.

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Section: Discussionmentioning

confidence: 99%

Unlocking the Molecular Secrets of Antifolate Drug Resistance: A Multi-Omics Investigation of the NCI-60 Cell Line Panel

Rushing

2023

Biomedicines

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“…Serine 2481 localizes at the regulatory domain of the kinase and could be involved in the modulation of its activity [8,9]. In mammalian cells mTOR exists as a core enzyme of two different complexes: mTORC1 and mTORC2 [13,14,15]. Earlier studies showed that specific mTOR inhibitor rapamycin treatment did not affect Serine 2481 phosphorilation.…”

Section: Discussionmentioning

confidence: 99%

Phospho-mTOR (Ser2481) colocalizes with condensed chromosomes during metaphase

et al. 2016

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Aim.To study the subcellular localization of phospho-mTOR (Ser2481) in cultured cells of human cancer cell lines. Methods. Immunofluorescent analysis of phospho-mTOR (Ser2481) subcellular localization in cultured MCF-7 (human breast adenocarcinoma) and HepG2 (human liver carcinoma) cells. Results. For the first time phospho-mTOR (Ser2481) was detected as bright spots situated in the equatorial region of chromosomes and co-localized with condensed chromosomes during metaphase. Conclusions. In this study, we describe for the first time the co-localization of phospho-mTOR (Ser2481) and chromosomes of the metaphase plate in the MCF-7 and HepG2 cells. Our data support the hypothesis that phospho-mTOR (Ser2481) could act as a CPP (chromosomal passenger protein)-like kinase, which takes part in the regulation of mitosis progression. K e y w o r d s: mTOR, phospho-mTOR (Ser2481), mitosis, mTOR phosphorylation, metaphase.

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“…mTORC1 localization is well characterized in mammalian cells. Newest data demonstrate a wide distribution of mTORC1 in the plasma membrane, cytosol, lysosome and the nucleus although in some cases the evidence is questionable [21][22][23]. In contrast to mTORC1, the mTORC2 localization is more obscure.…”

Section: Discussionmentioning

confidence: 99%

Association of Rictor with chromosomes during mitosis in MCF7 cells

Malanchuk

2015

Biopolym. Cell

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The mTOR kinase forms two multicomponent protein complexes (mTORC1 and mTORC2), where protein Rictor is a unique component of mTORC2. These two complexes differ both structurally and functionally and transmit signals to distinct downstream substrates. In contrast to mTORC1, comparatively little is known about functioning and regulation of mTORC2 and its components. Aim. The analysis of the particularity of Rictor subcellular localization in MCF7 cells. Methods. Immunofluorescence assay using confocal microscopy was applied. Results. Analysis of Rictor localization with anti N-terminal mAb revealed a different pattern of immunostaining in cells that was depended on cell cycle phase. For the first time it was shown that Rictor is at the exposed edge of condensed chromatin pool in MCF7 cells. Furthermore Z-stacking of cells revealed that character of association depends on mitosis phases. Conclusions. Our novel findings add to our understanding of functioning of both Rictor and mTORC2 in cell cycle progression.

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mTOR signaling and its involvement in the regulation of cell movements through remodeling the cytoskeleton architecture

Cited by 3 publications

References 48 publications

Unlocking the Molecular Secrets of Antifolate Drug Resistance: A Multi-Omics Investigation of the NCI-60 Cell Line Panel

Unlocking the Molecular Secrets of Antifolate Drug Resistance: A Multi-Omics Investigation of the NCI-60 Cell Line Panel

Phospho-mTOR (Ser2481) colocalizes with condensed chromosomes during metaphase

Association of Rictor with chromosomes during mitosis in MCF7 cells

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