ARG1 functions as a tumor suppressor in breast cancer

Ming, Zhengnan; Zou, Zizheng; Cai, Kaimei; Xu, Yunhua; Chen, Xueyan; Yi, Wei; Luo, Jun-Li; Luo, Zhitian

doi:10.1093/abbs/gmaa116

Cited by 9 publications

(7 citation statements)

References 35 publications

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“…Inhibitors of this pathway are streaming into different phases of clinical trials, and some of them have successfully made their way to the market. [ 61 ] Arg1, a cytosolic enzyme that catalyzes the hydrolysis of L‐arginine (Arg) to L‐ornithine and urea, [ 63 ] has also been regarded as a characteristic feature or a trigger of T cell exhaustion. [ 62 ] Its high expression is associated with poor prognosis in different types of cancers, including melanoma.…”

Section: Discussionmentioning

confidence: 99%

Nano‐Mediated PDT as a Multifunctional Immunomodulatory Agent in the Intricate Milieu of Melanoma

Sebak,

Abdel‐Halim,

Abdelrahman

et al. 2024

Advanced Therapeutics

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The complexity of the tumor microenvironment (TME) and nutrient competition represent the main causes of therapy resistance in cancers, including malignant melanoma (MM). Photodynamic therapy (PDT), through a cascade of events including its ability to induce significant immune responses, causes tumor eradication. However, the high pigmentation level of melanoma, lack of adequate accumulation of photosensitizers (PSs) in the target tissue as well as their nonspecific toxicity represent three main obstacles to obtaining satisfactory responses in melanoma. To prevail over these challenges, this study employed a depigmentation strategy followed by a nano‐mediated topical application of PDT using a chlorophyllin derivative as PS, focusing on evaluation of the immunomodulatory and metabolic regulatory axes of PDT in melanoma. Photo‐immunomodulation was assessed in a melanoma mouse model using a nanocarrier system of the PS. Markers of the immunosuppressive microenvironment and T cell exhaustion, as independent immune hallmarks, were quantified. The histopathology of spleen and skin/tumor was evaluated. The amino acid profile was quantified from normal skin or tumor biopsies using UHPLC‐MS/MS. Around 80% of the 300 nm transethosomal ferrous chlorophyllin (fC‐TEs) were retained in the tumor over 24 h upon topical application. Arbutin 2% gel not only decreased the melanin content of tumors, but also regulated the expression of interleukin 12 (IL‐12), IL‐10, transforming growth factor beta (TGF‐β) and tumor necrosis factor alpha (TNF‐α). Additionally, the nano‐mediated PDT strategy decreased the expression of programmed cell death protein 1 (PD‐1) & its ligand 1 (PD‐L1) and reduced the activity of arginase 1 (Arg1) through an upregulation of miRNA155. A mild recruitment of megakaryocytes (MKs) was observed in the spleen of the PDT group. This special localization of MKs depicts effector immune properties. Lastly, the combination of PDT and arbutin restored the normal tissue levels of arginine (Arg), glutamine (Gln) and lavished those of tryptophan (Trp). Nano‐mediated PDT represents a novel immunotherapeutic approach in melanoma by a triple modulation of the immune suppressive TME, immune checkpoint signaling, and reprogrammed tumor metabolism.This article is protected by copyright. All rights reserved

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Section: Discussionmentioning

confidence: 99%

Nano‐Mediated PDT as a Multifunctional Immunomodulatory Agent in the Intricate Milieu of Melanoma

Sebak,

Abdel‐Halim,

Abdelrahman

et al. 2024

Advanced Therapeutics

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“…Additionally, the level of Arg-1 decreases with high concentrations of L-norvaline, which functions as an Arg-1 inhibitor. Expression of Arg-1 leads to under-expression of p-AKT, resulting in deactivation of the AKT signaling pathway in BC cells; therefore, arg-1 acts as a tumor suppressor in BC [ 36 ]. The relationships between the abundance of Rothia genus, the level of norvaline, and the level of Arg-1 in breast tissue tumor requires further studies to understand the mechanism of the influence of Rothia and the metabolite norvaline on tumor growth.…”

Section: Discussionmentioning

confidence: 99%

Metagenomics Analysis of Breast Microbiome Highlights the Abundance of Rothia Genus in Tumor Tissues

Kartti

Bendani

Boumajdi

et al. 2023

JPM

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Breast cancer is one of the main global priorities in terms of public health. It remains the most frequent cancer in women and is the leading cause of their death. The human microbiome plays various roles in maintaining health by ensuring a dynamic balance with the host or in the appearance of various pathologies including breast cancer. In this study, we performed an analysis of bacterial signature differences between tumor and adjacent tissues of breast cancer patients in Morocco. Using 16S rRNA gene sequencing, we observed that adjacent tissue contained a much higher percentage of the Gammaproteobacteria class (35.7%) while tumor tissue was characterized by a higher percentage of Bacilli and Actinobacteria classes, with about 18.8% and 17.2% average abundance, respectively. Analysis of tumor subtype revealed enrichment of genus Sphingomonodas in TNBC while Sphingomonodas was predominant in HER2. The LEfSe and the genus level heatmap analysis revealed a higher abundance of the Rothia genus in tumor tissues. The identified microbial communities can therefore serve as potential biomarkers for prognosis and diagnosis, while also helping to develop new strategies for the treatment of breast cancer patients.

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“…Previous studies have shown that ARG1 is related to proliferation and migration in breast cancer and hepatocellular carcinoma (You et al, 2018;Ming et al, 2020). Therefore, we utilized western blotting and immunofluorescence to observe whether the proliferation or apoptosis of fetal lung cells was affected by Arg1 knockdown.…”

Section: Knockdown Of Arg1 In Fetal Lungs Induces Apoptosis Of Alveol...mentioning

confidence: 99%

Arginase 1 and L‐arginine coordinate fetal lung development and the initiation of labor in mice

Yu¹,

Liu²,

Sui³

et al. 2023

EMBO Reports

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Fetal development and parturition are precisely regulated processes that involve continuous crosstalk between the mother and the fetus. Our previous discovery that wild-type mice carrying steroid receptor coactivator (Src)-1 and Src-2 double-deficient fetuses exhibit impaired lung development and delayed labor, which indicates that the signals for parturition emanate from the fetus. In this study, we perform RNA sequencing and targeted metabolomics analyses of the lungs from fetal Src-1/-2 double-knockout mice and find that expression of arginase 1 (Arg1) is significantly decreased, accompanied by increased levels of the Arg1 substrate L-arginine. Knockdown of Arg1 in the lungs of fetal mice induces apoptosis of epithelial cells and dramatically delays initiation of labor. Moreover, treatment of human myometrial smooth muscle cells with L-arginine significantly inhibits spontaneous contractions by attenuating activation of NF-κB and downregulating expression of contraction-associated protein genes. Transcription factors GR and C/EBPβ increase transcription of Arg1 in an Src-1/Src-2-dependent manner. These findings provide new evidence that fetus-derived factors may play dual roles in coordinating fetal lung development and the initiation of labor.

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ARG1 functions as a tumor suppressor in breast cancer

Cited by 9 publications

References 35 publications

Nano‐Mediated PDT as a Multifunctional Immunomodulatory Agent in the Intricate Milieu of Melanoma

Nano‐Mediated PDT as a Multifunctional Immunomodulatory Agent in the Intricate Milieu of Melanoma

Metagenomics Analysis of Breast Microbiome Highlights the Abundance of Rothia Genus in Tumor Tissues

Arginase 1 and L‐arginine coordinate fetal lung development and the initiation of labor in mice

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