ArticlePloS one2013
Proteomic identification of mitochondrial targets of arginase in human breast cancer.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Loss of Arginase 2 Promotes Lung Metastasis in immune-competent hosts via Nitric Oxide Synthase 2-Dependent Th17 Response.bioRxiv : the preprint server for biology · 2026Article
- L-arginine metabolism in breast cancer: mechanisms and therapeutic targets.Frontiers in oncology · 2026Review
- Arginase Activity Inhibition With Thymoquinone Induces a Hybrid Type of Cell-Death in MDA-MB-231 Cell Line.Journal of biochemical and molecular toxicology · 2025Article
- Arginase-II promotes melanoma and lung cancer cell growth by regulating Sirt3-mtROS axis.Frontiers in cell and developmental biology · 2025Article
- pH responsive fabrication of PVA-stabilized selenium nano formulation encapsulated with luteolin to reduce diabetic ureteral injury by decreasing NLRP3 inflammasome via Nrf2/ARE signaling.Regenerative therapy · 2024Article
- Arginase-1 promotes lens epithelial-to-mesenchymal transition in different models of anterior subcapsular cataract.Cell communication and signaling : CCS · 2023Article
- One-Carbon and Polyamine Metabolism as Cancer Therapy Targets.Biomolecules · 2022Review
- Article
- Arginase 2 negatively regulates sorafenib-induced cell death by mediating ferroptosis in melanoma.Acta biochimica et biophysica Sinica · 2022Article
- OATD-02 Validates the Benefits of Pharmacological Inhibition of Arginase 1 and 2 in Cancer.Cancers · 2022Article
- Hyperpolarized [6-ACS chemical biology · 2019Article
- Design strategy for serine hydroxymethyltransferase probes based on retro-aldol-type reaction.Nature communications · 2019Article
- Rewiring urea cycle metabolism in cancer to support anabolism.Nature reviews. Cancer · 2018Review
- Major surgery diminishes systemic arginine availability and suppresses nitric oxide response to feeding in patients with early stage breast cancer.Clinical nutrition (Edinburgh, Scotland) · 2018Article
- Arginine and the metabolic regulation of nitric oxide synthesis in cancer.Disease models & mechanisms · 2018Review
- Peptidylarginine Deiminases-Roles in Cancer and Neurodegeneration and Possible Avenues for Therapeutic Intervention via Modulation of Exosome and Microvesicle (EMV) Release?International journal of molecular sciences · 2017Review
- High expression of apoptosis-inducing factor, mitochondrion-associated 3 (AIFM3) in human cholangiocarcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Increased sensitivity of African American triple negative breast cancer cells to nitric oxide-induced mitochondria-mediated apoptosis.BMC cancer · 2016Article
- Article
- The E3 ubiquitin ligase TRIM32 regulates myoblast proliferation by controlling turnover of NDRG2.Human molecular genetics · 2015Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
We have previously reported arginase expression in human breast cancer cells and demonstrated that the inhibition of arginase by N(ω) hydroxy L-arginine (NOHA) in MDA-MB-468 cells induces apoptosis. However, arginase expression and its possible molecular targets in human breast tumor samples and potential clinical implications have not been fully elucidated. Here, we demonstrate arginase expression in human breast tumor samples, and several established breast cancer cell lines, in which NOHA treatment selectively inhibits cell proliferation. The over-expression of Bcl2 in MDA-MB-468 cells abolished NOHA-induced apoptosis, suggesting that the mitochondria may be the main site of NOHA's action. We, therefore, undertook a proteomics approach to identify key mitochondrial targets of arginase in MDA-MB-468 cells. We identified 54 non-mitochondrial and 13 mitochondrial proteins that were differentially expressed in control and NOHA treated groups. Mitochondrial serine hydroxymethyltransferase (mSHMT) was identified as one of the most promising targets of arginase. Both arginase II (Arg II) and mSHMT expressions were higher in human breast tumor tissues compared to the matched normal and there was a strong correlation between Arg II and mSHMT protein expression. MDA-MB-468 xenografts had significant upregulation of Arg II expression that preceded the induction of mSHMT expression. Small inhibitory RNA (siRNA)-mediated inhibition of Arg II in MDA-MB-468 and HCC-1806 cells led to significant inhibition of both the mSHMT gene and protein expression. As mSHMT is a key player in folate metabolism, our data provides a novel link between arginine and folate metabolism in human breast cancer, both of which are critical for tumor cell proliferation.
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