Tag Archives: MTOR

Targeting Autophagy in Breast Cancer

Investigators present a review of autophagy focusing on its interplay with targeted drugs used for breast cancer treatment.
[International Journal of Molecular Sciences]
Cocco, S., Leone, A., Piezzo, M., Caputo, R., Di Lauro, V., Di Rella, F., Fusco, G., Capozzi, M., Gioia, G. di, Budillon, A., & De Laurentiis, M. (2020). Targeting Autophagy in Breast Cancer. International Journal of Molecular Sciences, 21(21), 7836. https://doi.org/10.3390/ijms21217836 Cite
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Macrophage-Derived Glutamine Boosts Satellite Cells and Muscle Regeneration

The uptake of macrophage-derived glutamine by satellite cells through the glutamine transporter SLC1A5 activated mTOR and promoted the proliferation and differentiation of satellite cells.
[Nature]
Shang, M., Cappellesso, F., Amorim, R., Serneels, J., Virga, F., Eelen, G., Carobbio, S., Rincon, M. Y., Maechler, P., De Bock, K., Ho, P.-C., Sandri, M., Ghesquière, B., Carmeliet, P., Di Matteo, M., Berardi, E., & Mazzone, M. (2020). Macrophage-derived glutamine boosts satellite cells and muscle regeneration. Nature, 1–6. https://doi.org/10.1038/s41586-020-2857-9 Cite
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Indole Hydrazide Compound ZJQ-24 Inhibits Angiogenesis and Induces Apoptosis Cell Death through Abrogation of AKT/mTOR Pathway in Hepatocellular Carcinoma

MTT assays, flow cytometric analysis, Western blotting and immunohistochemistry identified that ZJQ-24 effectively suppressed hepatocellular carcinoma cell proliferation via G2/M phase arrest and caspase-dependent apoptosis but had no cytotoxic on normal cells.
[Cell Death & Disease]
Liu, J., Liu, Y., Zhang, J., Liu, D., Bao, Y., Chen, T., Tang, T., Lin, J., Luo, Y., Jin, Y., & Zhang, J. (2020). Indole hydrazide compound ZJQ-24 inhibits angiogenesis and induces apoptosis cell death through abrogation of AKT/mTOR pathway in hepatocellular carcinoma. Cell Death & Disease, 11(10), 1–13. https://doi.org/10.1038/s41419-020-03108-2 Cite
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SCLC-CellMiner: A Resource for Small Cell Lung Cancer Cell Line Genomics and Pharmacology Based on Genomic Signatures

The authors demonstrated the reproducibility and stability of data from multiple sources and validate the small cell lung cancer (SCLC) consensus nomenclature on the basis of expression of master transcription factors NEUROD1, ASCL1, POU2F3, and YAP1.
[Cell Reports]
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Roles of Src Family Kinase, Ras, and mTOR Signaling in Intestinal Epithelial Homeostasis and Tumorigenesis

Dysregulation of intestinal epithelial cells(IEC) homeostasis likely contributes to the development of intestinal inflammation and intestinal cancer. The roles of receptor protein tyrosine kinases and their downstream signaling molecules such as Src family kinases, Ras, and mammalian target of rapamycin in homeostatic regulation of IEC turnover have recently been evaluated.
[Cancer Science]
Matozaki, T., Kotani, T., Murata, Y., & Saito, Y. (n.d.). Roles of Src family kinase, Ras, and mTOR signaling in intestinal epithelial homeostasis and tumorigenesis. Cancer Science, n/a(n/a). https://doi.org/10.1111/cas.14702 Cite
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BNIP3L/Nix-Induced Mitochondrial Fission, Mitophagy, and Impaired Myocyte Glucose Uptake Are Abrogated by PRKA/PKA Phosphorylation

In a series of gain-of-function and loss-of-function experiments in rodent and human myotubes, researchers demonstrated that BNIP3L accumulation triggers mitochondrial depolarization, calcium-dependent activation of DNM1L/DRP1, and mitophagy.
[Autophagy]
Rosa, S. C. da S., Martens, M. D., Field, J. T., Nguyen, L., Kereliuk, S. M., Hai, Y., Chapman, D., Diehl-Jones, W., Aliani, M., West, A. R., Thliveris, J., Ghavami, S., Rampitsch, C., Dolinsky, V. W., & Gordon, J. W. (2020). BNIP3L/Nix-induced mitochondrial fission, mitophagy, and impaired myocyte glucose uptake are abrogated by PRKA/PKA phosphorylation. Autophagy, 0(0), 1–16. https://doi.org/10.1080/15548627.2020.1821548 Cite
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A Ca2+-Dependent Switch Activates Axonal Casein Kinase 2α Translation and Drives G3BP1 Granule Disassembly for Axon Regeneration

Investigators showed that G3BP1 phosphorylation by casein kinase 2α (CK2α) triggered G3BP1 granule disassembly in injured axons. CK2α activity was temporally and spatially regulated by local translation of Csnk2a1 mRNA in axons after injury, but this required local translation of mTor mRNA and buffering of the elevated axonal Ca2+ that occurred after axotomy.
[Current Biology]
Sahoo, P. K., Kar, A. N., Samra, N., Terenzio, M., Patel, P., Lee, S. J., Miller, S., Thames, E., Jones, B., Kawaguchi, R., Coppola, G., Fainzilber, M., & Twiss, J. L. (2020). A Ca2+-Dependent Switch Activates Axonal Casein Kinase 2α Translation and Drives G3BP1 Granule Disassembly for Axon Regeneration. Current Biology, 0(0). https://doi.org/10.1016/j.cub.2020.09.043 Cite
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The Transcription Factor C/EBPβ Orchestrates Dendritic Cell Maturation and Functionality Under Homeostatic and Malignant Conditions

Investigators found that IL-33 expression in a large subset of human glioma specimens and murine models correlated with increased tumor-associated macrophages/monocytes/microglia. In addition, nuclear and secreted functions of IL-33 regulated chemokines that collectively recruit and activated circulating and resident innate immune cells creating a pro-tumorigenic environment.
[Proceedings of the National Academy of Sciences of the United States of America]
Scholz, F., Grau, M., Menzel, L., Graband, A., Zapukhlyak, M., Leutz, A., Janz, M., Lenz, G., Rehm, A., & Höpken, U. E. (2020). The transcription factor C/EBPβ orchestrates dendritic cell maturation and functionality under homeostatic and malignant conditions. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2008883117 Cite
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Increased Baseline RASGRP1 Signals Enhance Stem Cell Fitness during Native Hematopoiesis

The authors expanded RASGRP1 expression surveys in pediatric T-ALL and generated a RoLoRiG mouse model crossed to Mx1CRE to determine the consequences of induced RASGRP1 overexpression in primary hematopoietic cells.
[Oncogene]
Karra, L., Romero-Moya, D., Ksionda, O., Krush, M., Gu, Z., Mues, M., Depeille, P., Mullighan, C., & Roose, J. P. (2020). Increased baseline RASGRP1 signals enhance stem cell fitness during native hematopoiesis. Oncogene, 1–15. https://doi.org/10.1038/s41388-020-01469-8 Cite
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Translation Elongation Factor 2 Depletion by siRNA in Mouse Liver Leads to mTOR-Independent Translational Upregulation of Ribosomal Protein Genes

Researchers demonstrated the feasibility of perturbing protein synthesis in a mouse liver by targeting translation elongation factor 2 with RNAi. They were able to achieve over 90% knockdown efficacy and maintain it for two weeks effectively slowing down the rate of translation elongation.
[Scientific Reports]
Gerashchenko, M. V., Nesterchuk, M. V., Smekalova, E. M., Paulo, J. A., Kowalski, P. S., Akulich, K. A., Bogorad, R., Dmitriev, S. E., Gygi, S., Zatsepin, T., Anderson, D. G., Gladyshev, V. N., & Koteliansky, V. E. (2020). Translation elongation factor 2 depletion by siRNA in mouse liver leads to mTOR-independent translational upregulation of ribosomal protein genes. Scientific Reports, 10(1), 15473. https://doi.org/10.1038/s41598-020-72399-4 Cite
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PI3K/AKT Pathway as a Key Link Modulates the Multidrug Resistance of Cancers

The authors highlight the aberrant activation of PI3K/AKT as a key link that modulates multidrug resistance. They summarize the regulation of numerous major targets correlated with the PI3K/AKT pathway.
[Cell Death & Disease]
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