ArticleCell death discovery2025
TMEM45A enhances palbociclib resistance and cellular glycolysis by activating AKT/mTOR signaling pathway in HR+ breast cancer.
Article in Cell death discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed.
- Regulatory Role of Ribosome Biogenesis-Related Genes in Hepatocellular Carcinoma Prognosis and Construction of a Risk Prediction Model.Digestive diseases and sciences · 2026Article
- Alternative Splicing in Cyclin-Dependent Kinase 4/6 Inhibitor Resistance in Estrogen Receptor-Positive Breast Cancer.Drug development research · 2026Review
- TMEM92 shields DDX3X from TTC3-mediated degradation to confer chemoresistance in triple-negative breast cancer.Clinical and translational medicine · 2026Article
- TMEM132A is associated with metabolic reprogramming, macrophage-oriented immune remodeling, and breast cancer progression.Clinical and experimental medicine · 2026Article
- HES1 oscillations are required for cell cycle reentry in oestrogen receptor-positive breast cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- TGFβ signaling promotes cell cycle progression and resistance to the CDK4/6 inhibitor palbociclib through SOX4 transcriptional modulation in breast cancer cells.Cell death & disease · 2026Article
- TMEM45 protein family - Ancient residents of the cell endomembrane.Frontiers in molecular biosciences · 2026Review
- Research progress on TMEM proteins in cancer progression and chemoresistance (Review).International journal of molecular medicine · 2025Review
- PIK75 effectively reverses PI3K‒AKT activation caused by palbociclib resistance and synergistically inhibits the progression of esophageal squamous cell carcinoma.Scientific reports · 2025Article
- Emerging Mechanisms of Therapy Resistance in Metastatic ER+ Breast Cancer.Endocrinology · 2025Review
- Specific signaling pathways mediated programmed cell death in tumor microenvironment and target therapies.Discover oncology · 2025Review
- Role of EMT in drug resistance of breast cancer: molecular mechanisms and therapeutic strategies.Frontiers in oncology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Palbociclib, a CDK4/6 inhibitor, plays a crucial role in the treatment of HR+ breast cancer. However, resistance to palbociclib is a significant concern that merits further investigation. Our investigation identifies TMEM45A as a potential driver of palbociclib resistance and its association with increased cellular glycolysis. We demonstrate that TMEM45A is highly expressed in palbociclib-resistant breast cancer (BRCA) cells, correlating with enhanced tumor progression. Silencing TMEM45A enhances sensitivity to palbociclib, promotes cell cycle arrest and apoptosis, and inhibits the proliferation of BRCA cells. Moreover, attenuation of TMEM45A expression reduces cancer aggressiveness by decreasing the expression of EMT and glycolysis-related proteins. Subsequent gene set enrichment analysis (GSEA) confirms that TMEM45A activates the AKT/mTOR signaling pathway, which is integral to cell cycle progression and glycolysis. In a cell line-derived xenograft (CDX) mouse model, TMEM45A knockdown significantly restores sensitivity to palbociclib and suppresses tumor growth. Additionally, the use of engineered exosomes loaded with siRNA targeting TMEM45A presents a promising strategy for enhancing CDK4/6 inhibitor sensitivity without observable toxic side effects in a patient-derived xenograft (PDX) model. Collectively, our findings suggest that TMEM45A may be a therapeutic target for overcoming palbociclib resistance, and exosomal siRNA delivery could be a viable strategy for precision medicine in HR+ breast cancer.
Identifiers
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Registered trials
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.