Methionine dependence of virus-infected cells

Koziorowska, J; Mazurowa, Natalia; Tautt, J

doi:10.1016/0014-4827(90)90199-k

Cited by 7 publications

(5 citation statements)

References 16 publications

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“…The reprogramming of methionine metabolism (35) in cancer may be initiated by activated oncogenes as suggested by Vanhamme and Szpirer and Sacco et al (36, 37) where they showed that activated H-ras or K-ras oncogenes, when transfected into normal cells, caused them to become methionine dependent. It has also been shown that viral infection of normal cells induces methionine addiction (38). The reprogramming of methionine metabolism resulting in methionine addiction, histone H3 lysine overmethylation and malignancy may involve overexpression of specific histone H3 lysine methyltransferases (39).…”

Section: Discussionmentioning

confidence: 99%

The linkage of methionine addiction, overmethylation of histone H3 lysines and malignancy demonstrated when cancer cells revert to methionine-independence

Yamamoto

Inubushi²,

Han

et al. 2020

Preprint

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Methionine addiction is a fundamental and general hallmark of cancer. Methionine addiction results from the overuse of methionine by cancer cells for excess transmethylation reactions. In order to identify excess transmethylation reactions in cancer, we compared the histone H3 lysine methylation status between methionine-addicted cancer cells, normal cells and revertants of methionine-addicted cancer cells which regained methionine independence and lost malignancy. The levels of H3K4me3, H3K9me3 and pan-methyl lysine of histone H3 were elevated in methionine-addicted cancer cells in vitro compared to methionine-independent revertants isolated from the cancer cells and to normal cells. Tumorigenicity in nude mice was highly reduced in the methionine-independent revertants compared to the parental cells. The methionine-independent revertants no longer overmethylated pan-methyl lysine of H3, H3K4me3 and H3K9me3. Our previous studies showed that methionine restriction (MR) selectively arrests methionine-addicted cancer cells due to loss of histone H3 lysine methylation, which was stable in normal cells under MR. Our previous and present results suggest that overmethylation of histone H3 lysine is necessary for methionine addiction of cancer, required for the growth of cancer cells in vitro and in vivo, and necessary for malignancy. Methionine addiction has revealed fundamental molecular changes necessary for malignancy and presents great potential as a pan-cancer therapeutic target.Signiificance StatementAll cancer cell types are methionine-addicted. Methionine addiction is due to the overuse of methionine by cancer cells for excess transmethylation reactions. In the present study, we showed that the level of histone H3 lysine methylation was elevated in methionine-addicted cancer cells compared to normal fibroblasts and methionine-independent revertants with reduced malignancy that were derived from the methionine-addicted cancer cells. These results suggest that overmethylation of histone H3 lysine is necessary for methionine addiction of cancer and malignancy itself. Methionine addiction has revealed fundamental molecular changes necessary for malignancy and has been shown to be a universal therapeutic target in numerous pre-clinical studies of all major cancer types and has great clinical potential.

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Section: Discussionmentioning

confidence: 99%

The linkage of methionine addiction, overmethylation of histone H3 lysines and malignancy demonstrated when cancer cells revert to methionine-independence

Yamamoto

Inubushi²,

Han

et al. 2020

Preprint

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“…Second, during SARS-CoV-2 infection, T-cells and macrophages are over-activated, resulting in a huge increase in the level of cytokines (IL-1β, IL-6, TNF-α) and proteins associated with the macrophage. Upon this activation the T-cells also have an increased requirement for methionine [56]. The presence of T cells itself can be manifested by the 1094, 1325, 1372, 1452, and 1690 cm −1 bands, where their increased intensity ratios, with respect to the band at 1002 cm −1 for CoV(+) saliva, only prove the mentioned overactivation.…”

Section: Salivary Sers Fingerprint Of Covid-19mentioning

confidence: 99%

SERS Signature of SARS-CoV-2 in Saliva and Nasopharyngeal Swabs: Towards Perspective COVID-19 Point-of-Care Diagnostics

Berus

Nowicka

Wieruszewska

et al. 2023

IJMS

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In this study, the intrinsic surface-enhanced Raman spectroscopy (SERS)-based approach coupled with chemometric analysis was adopted to establish the biochemical fingerprint of SARS-CoV-2 infected human fluids: saliva and nasopharyngeal swabs. The numerical methods, partial least squares discriminant analysis (PLS-DA) and support vector machine classification (SVMC), facilitated the spectroscopic identification of the viral-specific molecules, molecular changes, and distinct physiological signatures of pathetically altered fluids. Next, we developed the reliable classification model for fast identification and differentiation of negative CoV(−) and positive CoV(+) groups. The PLS-DA calibration model was described by a great statistical value—RMSEC and RMSECV below 0.3 and R2cal at the level of ~0.7 for both type of body fluids. The calculated diagnostic parameters for SVMC and PLS-DA at the stage of preparation of calibration model and classification of external samples simulating real diagnostic conditions evinced high accuracy, sensitivity, and specificity for saliva specimens. Here, we outlined the significant role of neopterin as the biomarker in the prediction of COVID-19 infection from nasopharyngeal swab. We also observed the increased content of nucleic acids of DNA/RNA and proteins such as ferritin as well as specific immunoglobulins. The developed SERS for SARS-CoV-2 approach allows: (i) fast, simple and non-invasive collection of analyzed specimens; (ii) fast response with the time of analysis below 15 min, and (iii) sensitive and reliable SERS-based screening of COVID-19 disease.

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“…There are also promising studies showing that tumors are dependent on dietary metabolism and that methionine restriction can limit tumor growth in multiple models (Gao et al 2019). Viruses are also dependent on methionine for their growth; for example, cytomegalovirus (Koziorowska et al 1990), PR8 influenza (Ackermann & Kleinschmidt 1951), poliovirus (Mohajer & Gabliks 1966), and adenovirus (P.J. Mullen, W.B.…”

Section: Methioninementioning

confidence: 99%

The Metabolic Relationship Between Viral Infection and Cancer

Mullen

Christofk

2022

Annu. Rev. Cancer Biol.

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Viruses are fundamental tools in cancer research. They were used to discover the first oncogenes in the 1970s, and they are now being modified for use as antitumor therapeutics. Key to both of these oncogenic and oncolytic properties is the ability of viruses to rewire host cell metabolism. In this review, we describe how viral oncogenes alter metabolism to increase the synthesis of macromolecules necessary for both viral replication and tumor growth. We then describe how understanding the specific metabolic requirements of virus-infected cells can help guide strategies to improve the efficacy of oncolytic viruses, and highlight immunometabolism and tumor microenvironment research that could also increase the therapeutic benefits of oncolytic viruses. We also describe how studies describing the therapeutic effects of dietary nutrient restriction in cancer can suggest new avenues for research into antiviral therapeutics. Expected final online publication date for the Annual Review of Cancer Biology, Volume 6 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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Methionine dependence of virus-infected cells

Cited by 7 publications

References 16 publications

The linkage of methionine addiction, overmethylation of histone H3 lysines and malignancy demonstrated when cancer cells revert to methionine-independence

The linkage of methionine addiction, overmethylation of histone H3 lysines and malignancy demonstrated when cancer cells revert to methionine-independence

SERS Signature of SARS-CoV-2 in Saliva and Nasopharyngeal Swabs: Towards Perspective COVID-19 Point-of-Care Diagnostics

The Metabolic Relationship Between Viral Infection and Cancer

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