ArticleOncology letters2020
RRM2 elicits the metastatic potential of breast cancer cells by regulating cell invasion, migration and VEGF expression via the PI3K/AKT signaling.
Article in Oncology letters, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- RRM2 as a biomarker and therapeutic target in letrozole resistant estrogen receptor positive breast cancer.Scientific reports · 2026Article
- Decreased expression of ribonucleotide reductase M2 accelerates ovarian aging by suppressing cell proliferation and inducing DNA damage in mouse theca-interstitial cells.Journal of ovarian research · 2026Article
- Unveiling the Therapeutic Potential of Targeting RRM2 in Hepatocellular Carcinoma: An Integrated In Silico and In Vitro Study.Functional & integrative genomics · 2025Article
- Identification of modules and key genes associated with breast cancer subtypes through network analysis.Scientific reports · 2024Article
- Identification and validation of a metabolism-related gene signature for predicting the prognosis of paediatric medulloblastoma.Scientific reports · 2024Article
- Article
- CDC6 may serve as an indicator of lung adenocarcinoma prognosis and progression based on TCGA and GEO data mining and experimental analyses.Oncology reports · 2024Article
- Ribonucleotide reductase M2 (RRM2): Regulation, function and targeting strategy in human cancer.Genes & diseases · 2024Review
- Navigating the Blood-Brain Barrier: Challenges and Therapeutic Strategies in Breast Cancer Brain Metastases.International journal of molecular sciences · 2023Review
- Finding New Molecular Targets of Two Copper(II)-Hydrazone Complexes on Triple-Negative Breast Cancer Cells Using Mass-Spectrometry-Based Quantitative Proteomics.International journal of molecular sciences · 2023Article
- Over-expression of RRM2 predicts adverse prognosis correlated with immune infiltrates: A potential biomarker for hepatocellular carcinoma.Frontiers in oncology · 2023Article
- Hydroquinidine displays a significant anticarcinogenic activity in breast and ovarian cancer cells via inhibiting cell-cycle and stimulating apoptosis.Turkish journal of biology = Turk biyoloji dergisi · 2023Article
- Role of ferroptosis-related genes in coronary atherosclerosis and identification of key genes: integration of bioinformatics analysis and experimental validation.BMC cardiovascular disorders · 2022Article
- RRM2 enhances MYCN-driven neuroblastoma formation and acts as a synergistic target with CHK1 inhibition.Science advances · 2022Article
- MicroRNA-582-3p targeting ribonucleotide reductase regulatory subunit M2 inhibits the tumorigenesis of hepatocellular carcinoma by regulating the Wnt/β-catenin signaling pathway.Bioengineered · 2022Article
- Quality Analysis of YouTube Videos Presenting Shoulder Exercises after Breast Cancer Surgery.Breast care (Basel, Switzerland) · 2022Article
- LncRNA HOTAIR facilitates proliferation and represses apoptosis of retinoblastoma cells through the miR-20b-5p/RRM2/PI3K/AKT axis.Orphanet journal of rare diseases · 2022Article
- Angioregulatory microRNAs in breast cancerJournal of advanced research · 2022Review
- RRM2 expression in different molecular subtypes of breast cancer and its prognostic significance.Diagnostic pathology · 2022Article
- Ribonucleotide reductase subunit M2 promotes proliferation and epithelial-mesenchymal transition via the JAK2/STAT3 signaling pathway in retinoblastoma.Bioengineered · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Breast cancer is the second leading primary cause for cancer-related mortality among women and metastasis to the brain is a disastrous event for patients with increasing incidence. A previous study confirmed the critical function of RRM2 in breast cancer cell growth. Unfortunately, the role and fundamental molecular mechanism of RRM2 in breast cancer metastasis remains elusive. In the current study, higher RRM2 expression was validated in breast cancer tissues, especially in the brain metastasis group. Simultaneously, the expression of RRM2 was increased in breast cancer cells relative to the normal breast epithelial cell line MCF-10A, concomitant with higher levels of RRM2 in the highly metastatic MDA-MB-231 cell line relative to the weakly metastatic MCF-7 cell line. Knockdown of RRM2 by small interfering-RRM2 transfection notably suppressed the malignant metastatic behavior of breast cancer cells, including invasion and migration. Simultaneously, RRM2 downregulation also restrained the transcription and release of vascular endothelial growth factor (VEGF) in breast cancer cells. Moreover, inhibition of RRM2 dampened the activation of phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling by decreasing phosphorylated-AKT and downstream matrix metalloproteinases-2 expression. Intriguingly, reactivation of the PI3K/AKT pathway with its agonist insulin-like growth factor-1 reversed the adverse effects of RRM2 suppression on cancer cell invasion, migration and VEGF expression. Together, these findings suggest that RRM2 may act as a pro-metastatic factor to facilitate breast cancer metastasis by evoking cell invasion, migration and VEGF expression through the PI3K/AKT signaling pathway. This study may provide an attractive target for metastatic intervention in breast cancer.
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