ArticleBreast cancer research : BCR2023
S100A6 inhibits MDM2 to suppress breast cancer growth and enhance sensitivity to chemotherapy.
Article in Breast cancer research : BCR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 16 citations in OpenAlex.
- Let-7c-3p Suppresses Ovarian Cancer Progression by Targeting S100A6 and Inhibiting JAK-STAT Signaling.Cancers · 2026Article
- Helicobacter pylori Lipopolysaccharide Upregulates MDM2 via the TLR4/MAPK/AP-1 Pathway to Promote Gastric Cancer Progression.Digestive diseases and sciences · 2026Article
- STUB1 downregulates TOP2A through a dual mechanism of ubiquitination and FOXM1-mediated transcription repression, suppressing breast cancer growth and enhancing sensitivity to chemotherapy.Cellular & molecular biology letters · 2026Article
- Increased cytoplasmic and nuclear S100A6 expression is associated with improved prognosis in ovarian cancer.BMC cancer · 2026Article
- Single-cell and spatial transcriptomics reveal lactylation-associated tumor cell clusters and define a prognostic risk model in glioblastoma.BMC cancer · 2025Article
- Ubiquitination in cancer: mechanisms and therapeutic opportunities.Cancer communications (London, England) · 2025Review
- Research on the mechanism of GRIM-19 affecting lung adenocarcinoma through regulating MDM2 and EMT pathways.Cytotechnology · 2025Article
- The Conjugation of Paclitaxel with Chalcones for Enhancing Anti-tumor Activity.Current organic synthesis · 2025Article
- Spatial transcriptomics analysis identifies therapeutic targets in diffuse high-grade gliomas.Frontiers in molecular neuroscience · 2024Article
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6 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundS100A6 and murine double minute 2 (MDM2) are important cancer-related molecules. A previous study identified an interaction between S100A6 and MDM2 by size exclusion chromatography and surface plasmon resonance experiments. The present study investigated whether S100A6 could bind to MDM2 in vivo and further explored its functional implication.
methodsCo-immunoprecipitation, glutathione-S-transferase pull-down assay, and immunofluorescence were performed to determine the in vivo interaction between S100A6 and MDM2. Cycloheximide pulse-chase assay and ubiquitination assay were performed to clarify the mechanism by which S100A6 downregulated MDM2. In addition, clonogenic assay, WST-1 assay, and flow cytometry of apoptosis and the cell cycle were performed and a xenograft model was established to evaluate the effects of the S100A6/MDM2 interaction on growth and paclitaxel-induced chemosensitivity of breast cancer. The expressions of S100A6 and MDM2 in patients with invasive breast cancer were analyzed by immunohistochemistry. In addition, the correlation between the expression of S100A6 and the response to neoadjuvant chemotherapy was statistically analyzed.
resultsS100A6 promoted the MDM2 translocation from nucleus to cytoplasm, in which the S100A6 bound to the binding site of the herpesvirus-associated ubiquitin-specific protease (HAUSP) in MDM2, disrupted the MDM2-HAUSP-DAXX interactions, and induced the MDM2 self-ubiquitination and degradation. Furthermore, the S100A6-mediated MDM2 degradation suppressed the growth of breast cancer and enhanced its sensitivity to paclitaxel both in vitro and in vivo. For patients with invasive breast cancer who received epirubicin and cyclophosphamide followed by docetaxel (EC-T), expressions of S100A6 and MDM2 were negatively correlated, and high expression of S100A6 suggested a higher rate of pathologic complete response (pCR). Univariate and multivariate analyses showed that the high expression of S100A6 was an independent predictor of pCR.
conclusionThese results reveal a novel function for S100A6 in downregulating MDM2, which directly enhances sensitivity to chemotherapy.
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