ArticleCell cycle (Georgetown, Tex.)2013
Cell cycle regulators cyclin D1 and CDK4/6 have estrogen receptor-dependent divergent functions in breast cancer migration and stem cell-like activity.
Article in Cell cycle (Georgetown, Tex.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 90 citations in OpenAlex.
- Histone acetyltransferase HBO1 in cancer biology: Essential mechanisms and implications for targeted therapeutics.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Tumor cell cycle regulation: integrated perspective of stage characteristics, regulatory networks, and signaling pathway intervention strategies.Molecular biomedicine · 2026Review
- Bioinformatics-based multi-omics and machine learning analysis identifies stemness-associated molecular subtypes and a prognostic index in breast cancer.Translational cancer research · 2025Article
- Mechanism and Predictive Role of NUB1 Protein in Oestrogen Receptor Pathway of FEC-Treated Breast Cancer Patients.Biomedicines · 2025Article
- Proteogenomic discovery ofScience advances · 2025Article
- Quercetin promotes production of secondary hair follicle stem cells in cashmere goat: a mechanistic study.Frontiers in veterinary science · 2025Article
- Novel indolyl 1,2,4-triazole derivatives as potential anti-proliferative agents:RSC medicinal chemistry · 2024Article
- 2-methoxyestradiol inhibits the malignant behavior of triple negative breast cancer cells by altering their miRNome.Frontiers in oncology · 2024Article
- A review of prognostic and predictive biomarkers in breast cancer.Clinical and experimental medicine · 2023Review
- Role of eIF4A1 in triple-negative breast cancer stem-like cell-mediated drug resistance.Cancer reports (Hoboken, N.J.) · 2022Article
- Triphenyl phosphate activates estrogen receptor α/NF-κB/ cyclin D1 signaling to stimulate cell cycle progression in human Ishikawa endometrial cancer cells.Obstetrics & gynecology science · 2022Article
- Drug Resistance in Metastatic Breast Cancer: Tumor Targeted Nanomedicine to the Rescue.International journal of molecular sciences · 2021Review
- Differential reprogramming of breast cancer subtypes in 3D cultures and implications for sensitivity to targeted therapy.Scientific reports · 2021Article
- [Identification of Hub Genes for Ovarian Cancer Stem Cell Properties with Weighted Gene Co-expression Network Analysis].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2021Article
- A Cyclin D1-Dependent Transcriptional Program Predicts Clinical Outcome in Mantle Cell Lymphoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- HSulf‑1 and palbociclib exert synergistic antitumor effects on RB‑positive triple‑negative breast cancer.International journal of oncology · 2020Article
- Identification of key genes controlling breast cancer stem cell characteristics via stemness indices analysis.Journal of translational medicine · 2020Article
- Abnormal spindle-like microcephaly-associated protein (ASPM) contributes to the progression of Lung Squamous Cell Carcinoma (LSCC) by regulating CDK4.Journal of Cancer · 2020Article
- CRABP2 regulates invasion and metastasis of breast cancer through hippo pathway dependent on ER status.Journal of experimental & clinical cancer research : CR · 2019Article
- Decoding the link between WWOX and p53 in aggressive breast cancer.Cell cycle (Georgetown, Tex.) · 2019Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclin D1 and its binding partners CDK4/6 are essential regulators of cell cycle progression and are implicated in cancer progression. Our aim was to investigate a potential regulatory role of these proteins in other essential tumor biological characteristics. Using a panel of breast cancer cell lines and primary human breast cancer samples, we have demonstrated the importance of these cell cycle regulators in both migration and stem-like cell activity. siRNA was used to target cyclin D1 and CDK4/6 expression, having opposing effects on both migration and stem-like cell activity dependent upon estrogen receptor (ER) expression. Inhibition of cyclin D1 or CDK4/6 increases or decreases migration and stem-like cell activity in ER-ve (ER-negative) and ER+ve (ER-positive) breast cancer, respectively. Furthermore, overexpressed cyclin D1 caused decreased migration and stem-like cell activity in ER-ve cells while increasing activity in ER+ve breast cancer cells. Treatment of breast cancer cells with inhibitors of cyclin D1 and CDK4/6 (Flavopiridol/PD0332991), currently in clinical trials, mimicked the effects observed with siRNA treatment. Re-expression of ER in two ER-ve cell lines was sufficient to overcome the effects of either siRNA or clinical inhibitors of cyclin D1 and CDK4/6. In conclusion, cyclin D1 and CDK4/6 have alternate roles in regulation of migration and stem-like cell activity. Furthermore, these effects are highly dependent upon expression of ER. The significance of these results adds to our general understanding of cancer biology but, most importantly, could be used diagnostically to predict treatment response to cell cycle inhibition in breast cancer.
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