Targeting PRMT1 reduces cancer persistence and tumor relapse in EGFR- and KRAS-mutant lung cancer DOI Creative Commons
Xiaoxiao Sun, Karl Kumbier,

Savitha Gayathri

et al.

Cancer Research Communications, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 19, 2024

Incomplete killing of cancer cells undermines oncogene-targeting therapies and drives disease relapse. Eliminating that persist during treatment is crucial for improving outcomes. Here, we discovered a specific isoform type I protein arginine methyltransferases (PRMTs), namely PRMT1, enables lung with EGFR or KRASG12C driver mutations high STAT1 activity to through targeted drug treatments. PRMT1 knockdown, combined inhibitors, decreased persistence delayed cell regrowth across line models significantly prolonged tumor regression in xenograft models. In contrast, found knockdown two other PRMT isoforms, PRMT4 PRMT6, increased persistence. Finally, targeting reduce more effective intact vs. deleted chromosome 5q31.1, region enriched JAK-STAT pathway genes, suggesting potential stratification criterion. Together, our study pinpoints the as critical vulnerability EGFR- KRASG12C-targeted therapies.

Language: Английский

DNA-Binding Agent Trabectedin Combined With Recombinant Methioninase Is Synergistic to Decrease Fibrosarcoma Cell Viability and Induce Nuclear Fragmentation But Not Synergistic on Normal Fibroblasts DOI Creative Commons
Sei Morinaga,

Qinghong Han,

YUTARO KUBOTA

et al.

Anticancer Research, Journal Year: 2024, Volume and Issue: 44(6), P. 2359 - 2367

Published: May 31, 2024

Background/Aim: The alkylating agent trabectedin, which binds the minor groove of DNA, is second-line therapy for soft-tissue sarcoma but has only moderate efficacy. aim present study was to determine synergistic efficacy recombinant methioninase (rMETase) and trabectedin on fibrosarcoma cells in vitro, compared with normal fibroblasts. Materials Methods: HT1080 human expressing green fluorescent protein (GFP) nucleus red (RFP) cytoplasm Hs27 fibroblasts, were used. Each cell line cultured vitro divided into four groups: no-treatment control; treated; rMETase plus treated. dual-color used quantitate nuclear fragmentation each treatment group. Results: combination highly decrease viability. In contrast, there no synergy cells. Moreover, occurred synergistically Conclusion: suggesting that can improve outcome alone future clinical studies. lack fibroblasts suggests not toxic Synergy two drugs may be due high rate treated cells, late-S/G2 cell-cycle block cancer by rMETase, a target trabectedin. results suggest potential sarcoma.

Language: Английский

Citations

5
Recombinant Methioninase Is Selectively Synergistic With Doxorubicin Against Wild-type Fibrosarcoma Cells Compared to Normal Cells and Overcomes Highly-Doxorubicin-resistant Fibrosarcoma DOI Creative Commons
Sei Morinaga,

QINGHONG HAN,

KOHEI MIZUTA

et al.

Anticancer Research, Journal Year: 2024, Volume and Issue: 44(8), P. 3261 - 3268

Published: July 26, 2024

Background/Aim: Doxorubicin is first-line therapy for soft-tissue sarcoma, but patients can develop resistance which usually fatal. As a novel therapeutic strategy, the present study aimed to determine synergy of recombinant methioninase (rMETase) and doxorubicin against HT1080 fibrosarcoma cells compared Hs27 normal fibroblasts, rMETase efficacy doxorubicin-resistant in vitro. Materials Methods: The 50% inhibitory concentrations (IC50) rMETase, as well their combination efficacy, human cells, fibroblasts (DR-HT1080) were determined. Dual-color expressed red fluorescent protein (RFP) cytoplasm green (GFP) nuclei used visualize nuclear fragmentation during treatment. Nuclear was observed with an IX71 fluorescence microscope. Results: IC50 3.3 μM 12.4 DR-HT1080 7.25 cells. 0.75 U/ml 0.42 0.93 synergistic not fibroblasts. plus also caused more fragmented than either treatment alone highly effective parental Conclusion: results indicate future clinical potential fibrosarcoma, including fibrosarcoma.

Language: Английский

Citations

4
A Methionine Allocation Nanoregulator for the Suppression of Cancer Stem Cells and Support to the Immune Cells by Epigenetic Regulation DOI Creative Commons

Boyu Su,

Qinjun Chen, Xu‐Wen Li

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 22, 2025

Abstract Epigenetic dysregulation is prevalent in human cancers, affecting gene expression and metabolic patterns to meet the demands of malignant evolution abnormal epigenetic processes, resulting a protumor immune microenvironment. Tumors require steady supply methionine for maintaining flexibility, which only exogenous precursor methyl donor S‐adenosylmethionine methylation, crucial their resistance therapies survival nutrient‐deficient Thus, tumor cells upregulate Lat4 transporter compete deprive microenvironment, sustaining phenotypes also impairing cell functions. Addressing this addiction key overcoming drug improving response. Despite challenge lacking specific inhibitors, an oxaliplatin prodrug crosslinked fluorinated polycation/anti‐Lat4 small interfering RNA complex nanoregulator (AS‐F‐NP) has been designed developed here. This restricted greedy uptake by knocking down Lat4, turn inhibited while restoring viability function tumor‐infiltrating cells.

Language: Английский

Citations

0
Metabolic Reprogramming of Tumor Microenviroment by Engineered Bacteria DOI
Heng Wang, Fang Xu, Chao Wang

et al.

Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Methionine-Specific Bioconjugation for Single-Molecule Force Spectroscopy of Cell Surface Proteins DOI
Junsheng Zhang, Yang Li,

Luofei Li

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Cell surface proteins play crucial roles in various cellular processes, including intercellular communication, adhesion, and immune responses. However, investigating these using single-molecule force spectroscopy (SMFS) has been hindered by challenges site-specific protein modification while preserving their native state. Here, we introduce a methionine-specific bioconjugation strategy utilizing bespoke hypervalent iodine reagent for highly selective, rapid, robust methionine labeling. Since is often the first amino acid incorporated into via initiator tRNA, this approach enables precise N-terminal labeling attachment, facilitating more reliable SMFS studies. The resulting covalent linkage remains intact during mechanical unfolding or conformational changes of proteins, with stability exceeding 600 pN, allowing accurate measurements before detachment from AFM cantilever tips cell surfaces. Additionally, method improves sampling rates data quality. We successfully applied technique to light-induced printing natural studies, demonstrating its potential advancing mechanics research living cells. This provides significant advantages study complex systems.

Language: Английский

Citations

0
Unveiling the crossroads of STING signaling pathway and metabolic reprogramming: the multifaceted role of the STING in the TME and new prospects in cancer therapies DOI Creative Commons
Siwei Wang, Qin Lu, Furong Liu

et al.

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 7, 2025

The cGAS-STING signaling pathway serves as a critical link between DNA sensing and innate immunity, has tremendous potential to improve anti-tumor immunity by generating type I interferons. However, STING agonists have shown decreasing biotherapeutic efficacy in clinical trials. Tumor metabolism, characterized aberrant nutrient utilization energy production, is fundamental hallmark of tumorigenesis. And modulating metabolic pathways tumor cells been discovered therapeutic strategy for tumors. As research concerning progressed, emerging evidence highlights its role reprogramming, independent immune function, indicating targets activation cancers. In this review, we delve into the interplay multiple pathways. We also synthesize current knowledge on antitumor functions STING, within microenvironment (TME) that could be exploited activation. This review necessity future dissect complex interactions with various cancer types, emphasizing personalized strategies based profiling.

Language: Английский

Citations

0
Overcoming High Trabectedin Resistance of Soft-tissue Sarcoma With Recombinant Methioninase: A Potential Solution of a Recalcitrant Clinical Problem DOI Creative Commons
Sei Morinaga,

Qinghong Han,

KOHEI MIZUTA

et al.

Anticancer Research, Journal Year: 2024, Volume and Issue: 44(9), P. 3785 - 3791

Published: Aug. 28, 2024

Drug resistance has been a recalcitrant problem for sarcoma patients many decades. Trabectedin is second-line chemotherapy soft-tissue that often leads to and death of the patients. The objective present study was address issue trabectedin-chemoresistance in HT1080 fibrosarcoma cells by combining recombinant methioninase (rMETase) with trabectedin examining their efficacy on trabectedin-resistant vitro.

Language: Английский

Citations

2
Recombinant Methioninase Increases Eribulin Efficacy 16-fold in Highly Eribulin-resistant HT1080 Fibrosarcoma Cells, Demonstrating Potential to Overcome the Clinical Challenge of Drug-resistant Soft-tissue Sarcoma DOI Creative Commons
Sei Morinaga,

Qinghong Han,

KOHEI MIZUTA

et al.

Anticancer Research, Journal Year: 2024, Volume and Issue: 44(9), P. 3777 - 3783

Published: Aug. 28, 2024

A major challenge in treating soft-tissue sarcoma is the development of drug resistance. Eribulin, an anti-tubulin agent, used as a second-line chemotherapy for patients with unresectable or metastatic sarcoma. However, most advanced are resistant to eribulin and do not survive. Recombinant methioninase (rMETase) targets fundamental general hallmark cancer, methionine addiction, termed Hoffman Effect. The present study aimed show how much rMETase could increase efficacy on eribulin-resistant fibrosarcoma cells vitro.

Language: Английский

Citations

2
The Combination of Methionine Restriction and Docetaxel Synergistically Arrests Androgen-independent Prostate Cancer But Not Normal Cells DOI

KOHEI MIZUTA,

Ryosuke Mori,

Qinghong Han

et al.

Cancer Diagnosis & Prognosis, Journal Year: 2024, Volume and Issue: 4(4), P. 402 - 407

Published: July 1, 2024

Androgen-independent prostate cancer (AIPC) is resistant to androgen-depletion therapy and a recalcitrant disease. Docetaxel the first-line treatment for AIPC, but has limited efficacy severe side-effects. All cancers are methionine-addicted, which termed Hoffman effect. Recombinant methioninase (rMETase) targets methionine addiction. The purpose of present study was determine if combination docetaxel rMETase effective AIPC.

Language: Английский

Citations

1
Synergy of Rapamycin and Methioninase on Colorectal Cancer Cells Requires Simultaneous and Not Sequential Administration: Implications for mTOR Inhibition DOI

DANIEL ARDJMAND,

MOTOKAZU SATO,

Qinghong Han

et al.

Cancer Diagnosis & Prognosis, Journal Year: 2024, Volume and Issue: 4(4), P. 396 - 401

Published: July 1, 2024

Rapamycin inhibits the mTOR protein kinase. Methioninase (rMETase), by degrading methionine, targets methionine addiction of cancer cells and has been shown to improve efficacy chemotherapy drugs, reducing their effective doses. Our previous study demonstrated that rapamycin rMETase work synergistically against colorectal-cancer cells, but not on normal when administered simultaneously in vitro. In present study, we aimed further our findings exploring whether synergy exists between used sequentially HCT-116 colorectal-carcinoma compared simultaneous administration,

Language: Английский

Citations

0