ArticleCell biochemistry and biophysics2024
TYMS Knockdown Suppresses Cells Proliferation, Promotes Ferroptosis via Inhibits PI3K/Akt/mTOR Signaling Pathway Activation in Triple Negative Breast Cancer.
Article in Cell biochemistry and biophysics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Repurposing Lapatinib and Tucatinib as Dual Inhibitors of Bcl-2 and TYMS in Breast Cancer: Insights from Transcriptomic, Computational and Cellular Assays.Applied biochemistry and biotechnology · 2026Article
- M2 Macrophage-Derived Exosomes Ameliorate BPD by Inhibiting Ferroptosis via Suppression of the ZAKα-p38 Signaling Pathway.Antioxidants (Basel, Switzerland) · 2026Article
- Indirubin treatment was associated with modulation of the PI3K/AKT and MAPK pathways and induction of apoptosis and autophagy.Scientific reports · 2026Article
- KIF14-AKT axis regulates ferroptosis sensitivity in triple-negative breast cancer.Open life sciences · 2026Article
- Characterization of Differential GPX4 Essentiality Between Intrahepatic and Extrahepatic Cholangiocarcinoma via Leveraging of a Large-Scale Functional Genomic Screen.International journal of molecular sciences · 2025Article
- Scutellarin triggers ferroptosis in ovarian cancer cells via inhibiting AKT/mTOR and JAK2/STAT3 pathways.Medical oncology (Northwood, London, England) · 2025Article
- Natural Compounds as Modulators of Ferroptosis: Mechanistic Insights and Therapeutic Prospects in Breast Cancer.Biomolecules · 2025Review
- Treatment strategies targeting the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin pathway against triple-negative breast cancer.World journal of clinical oncology · 2025Review
- Iron-Dependent Cell Death: Exploring Ferroptosis as a Unique Target in Triple-Negative Breast Cancer Management.Cancer management and research · 2025Review
- Unveiling the oncogenic significance of thymidylate synthase in human cancers.American journal of translational research · 2024Article
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Authors and funding
9 authors.
Funding
Abstract
Triple-negative breast cancer (TNBC) is characterized by a grim prognosis and numerous challenges. The objective of our study was to examine the role of thymidylate synthase (TYMS) in TNBC and its impact on ferroptosis. The expression of TYMS was analyzed in databases, along with its prognostic correlation. TYMS positive expression was identified through immunohistochemistry (IHC), while real-time quantitative PCR (qRTPCR) was employed to measure TYMS mRNA levels in various cell lines. Western blotting was utilized to assess protein expression. Cell proliferation, mobility, apoptosis, and reactive oxygen species (ROS) levels were evaluated using CCK8, wound scratch healing assay, transwell assay, and flow cytometry, respectively. Additionally, a tumor xenograft model was established in BALB/c nude mice for further investigation. Tumor volume and weight were measured, and histopathological analysis using hematoxylin and eosin (H&E) staining was conducted to assess tumor tissue changes. IHC staining was employed to detect the expression of Ki67 in tumor tissues. High expression of TYMS was observed in TNBC and was found to be correlated with poor prognosis in patients. Among various cell lines, TYMS expression was highest in BT549 cells. Knockdown of TYMS resulted in suppression of cell proliferation and mobility, as well as promotion of apoptosis. Furthermore, knockdown of TYMS led to increased accumulation of ROS and Fe2+ levels, along with upregulation of ACLS4 expression and downregulation of glutathione peroxidase 4 (GPX4) expression. In vivo studies showed that knockdown of TYMS inhibited tumor growth. Additionally, knockdown of TYMS was associated with inhibition of mTOR, p-PI3K, and p-Akt expression. Our research showed that the knockdown of TYMS suppressed the TNBC progression by inhibited cells proliferation via ferroptosis. Its underlying mechanism is related to the PI3K /Akt pathway. Our study provides a novel sight for the suppression effect of TYMS on TNBC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.