ArticleOncogene2014
Pin1 modulates ERα levels in breast cancer through inhibition of phosphorylation-dependent ubiquitination and degradation.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 68 citations in OpenAlex.
- Nucleic sexual hormone receptor signaling pathways in breast cancer: function regulation, crosstalk, and therapeutic implications.NPJ precision oncology · 2026Review
- Neuronal UBE3A substrates hold therapeutic potential for Angelman syndrome.Current opinion in neurobiology · 2024Review
- UBE2M forms a positive feedback loop with estrogen receptor to drive breast cancer progression and drug resistance.Cell death & disease · 2024Article
- Review
- Discovery of potent PROTAC degraders of Pin1 for the treatment of acute myeloid leukemia.Chemical science · 2024Article
- Overexpression of TPL2 may be a predictor of good prognosis in patients with breast invasive ductal carcinoma.Scientific reports · 2023Article
- Decoding the Therapeutic Implications of the ERα Stability and Subcellular Distribution in Breast Cancer.Frontiers in endocrinology · 2022Review
- Calcineurin regulates the stability and activity of estrogen receptor α.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Targeting Pin1 for Modulation of Cell Motility and Cancer Therapy.Biomedicines · 2021Review
- Review
- Review
- Differential Regulation and Targeting of Estrogen Receptor α Turnover in Invasive Lobular Breast Carcinoma.Endocrinology · 2020Article
- Estrogen Receptors and Ubiquitin Proteasome System: Mutual Regulation.Biomolecules · 2020Review
- Pinning Down the Transcription: A Role for Peptidyl-ProlylFrontiers in cell and developmental biology · 2020Review
- Function of PIN1 in Cancer Development and Its Inhibitors as Cancer Therapeutics.Frontiers in cell and developmental biology · 2020Review
- Hypoxia differentially regulates estrogen receptor alpha in 2D and 3D culture formats.Archives of biochemistry and biophysics · 2019Article
- Targeting Pin1 by All-Trans Retinoic Acid (ATRA) Overcomes Tamoxifen Resistance in Breast Cancer via Multifactorial Mechanisms.Frontiers in cell and developmental biology · 2019Article
- GPCR Modulation in Breast Cancer.International journal of molecular sciences · 2018Review
- Prolyl isomerase Pin1: a promoter of cancer and a target for therapy.Cell death & disease · 2018Review
- Polyubiquitination inhibition of estrogen receptor alpha and its implications in breast cancer.World journal of clinical oncology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Estrogen receptor-alpha (ERα) is an important biomarker used to classify and direct therapy decisions in breast cancer (BC). Both ERα protein and its transcript, ESR1, are used to predict response to tamoxifen therapy, yet certain tumors have discordant levels of ERα protein and ESR1, which is currently unexplained. Cellular ERα protein levels can be controlled post-translationally by the ubiquitin-proteasome pathway through a mechanism that depends on phosphorylation at residue S118. Phospho-S118 (pS118-ERα) is a substrate for the peptidyl prolyl isomerase, Pin1, which mediates cis-trans isomerization of the pS118-P119 bond to enhance ERα transcriptional function. Here, we demonstrate that Pin1 can increase ERα protein without affecting ESR1 transcript levels by inhibiting proteasome-dependent receptor degradation. Pin1 disrupts ERα ubiquitination by interfering with receptor interactions with the E3 ligase, E6AP, which also is shown to bind pS118-ERα. Quantitative in situ assessments of ERα protein, ESR1, and Pin1 in human tumors from a retrospective cohort show that Pin1 levels correlate with ERα protein but not to ESR1 levels. These data show that ERα protein is post-translationally regulated by Pin1 in a proportion of breast carcinomas. As Pin1 impacts both ERα protein levels and transactivation function, these data implicate Pin1 as a potential surrogate marker for predicting outcome of ERα-positive BC.
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What OpenQuestion holds
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.