ArticleNature communications2018
LEM4 confers tamoxifen resistance to breast cancer cells by activating cyclin D-CDK4/6-Rb and ERα pathway.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50 citing papers in PubMed, 70 citations in OpenAlex.
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- The Roles of MicroRNAs, Oncogenes, and Tumor Suppressor Gene Molecular Subtypes of Breast Cancer: Therapeutic Potential of Pharmaceutical and Natural Products.International journal of breast cancer · 2026Review
- Nuclear envelope proteins in cancer: revisiting the significance of LEM-domain proteins.Frontiers in cell and developmental biology · 2026Review
- LEM4 interacts with β-catenin and promotes β-catenin-dependent transcription activity to confers ribociclib resistance in breast cancer cells.Scientific reports · 2025Article
- ATE1 promotes breast cancer progression via arginylation-dependent regulation of MAPK-MYC signaling.Cell communication and signaling : CCS · 2025Article
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- Investigation of circulating miR-182-3p, miR -382-3p and miR -93, miR -142-3p involved in tamoxifen resistance and sensitivity in luminal-subtype breast cancer patients: a case-control study.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
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- The significant others of aurora kinase a in cancer: combination is the key.Biomarker research · 2024Review
- Reversal of the tamoxifen‑resistant breast cancer malignant phenotype by proliferation inhibition with bromosulfonamidine amino‑podophyllotoxin.Oncology letters · 2024Article
- Dexamethasone-tamoxifen combination exerts synergistic therapeutic effects in tamoxifen-resistance breast cancer cells.Bioscience reports · 2024Article
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- Article
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Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The elucidation of molecular events that confer tamoxifen resistance to estrogen receptor α (ER) positive breast cancer is of major scientific and therapeutic importance. Here, we report that LEM4 overexpression renders ER+ breast cancer cells resistant to tamoxifen by activating the cyclin D-CDK4/6 axis and the ERα signaling. We show that LEM4 overexpression accelerates tumor growth. Interaction with LEM4 stabilizes CDK4 and Rb, promotes Rb phosphorylation and the G1/S phase transition. LEM4 depletion or combined tamoxifen and PD0332991 treatment significantly reverses tamoxifen resistance. Furthermore, LEM4 interacts with and stabilizes both Aurora-A and ERα, promotes Aurora-A mediated phosphorylation of ERα-Ser167, leading to increase in ERα DNA-binding and transactivation activity. Elevated levels of LEM4 correlates with poorer relapse-free survival in patients with ER+ breast cancer undergoing endocrine therapy. Thus, LEM4 represents a prognostic marker and an attractive target for breast cancer therapeutics. Functional antagonism of LEM4 could overcome tamoxifen resistance.
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