ArticleScience translational medicine2014
Epigenetic reprogramming of HOXC10 in endocrine-resistant breast cancer.
Article in Science translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Prosaposin activates the androgen receptor and potentiates resistance to endocrine treatment in breast cancer.Breast cancer research : BCR · 2015Pooled it
- S100β as a serum marker in endocrine resistant breast cancer.BMC medicine · 2017Trial
- EZH2 blockade reverses doxorubicin resistance by inducing metabolic vulnerability and enhancing DNA damage in breast cancer.Frontiers in pharmacology · 2026Article
- The HOXC10/NOD1/ERK axis drives osteolytic bone metastasis of pan-KRAS-mutant lung cancer.Bone research · 2024Article
- mInternational journal of oncology · 2024Article
- Article
- MDiscover oncology · 2023Article
- Cuproptosis/ferroptosis-related gene signature is correlated with immune infiltration and predict the prognosis for patients with breast cancer.Frontiers in pharmacology · 2023Article
- Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis.Nature cancer · 2023Article
- Molecular implications of HOX genes targeting multiple signaling pathways in cancer.Cell biology and toxicology · 2022Review
- The expression ofAnnals of translational medicine · 2022Article
- Type 1 Nuclear Receptor Activity in Breast Cancer: Translating Preclinical Insights to the Clinic.Cancers · 2021Review
- HOXC10 promotes growth and migration of melanoma by regulating Slug to activate the YAP/TAZ signaling pathway.Discover oncology · 2021Article
- Distinct Shades of Adipocytes Control the Metabolic Roles of Adipose Tissues: From Their Origins to Their Relevance for Medical Applications.Biomedicines · 2021Review
- ARID1A Mutation in Metastatic Breast Cancer: A Potential Therapeutic Target.Frontiers in oncology · 2021Review
- Homeobox Genes in Cancers: From Carcinogenesis to Recent Therapeutic Intervention.Frontiers in oncology · 2021Review
- Role of HOXC10 in Cancer.Frontiers in oncology · 2021Review
- Low HOXC10 expression in liver cancer regulates proliferation via a mechanism involving miR-221 and the MAPK signaling pathway.Oncology letters · 2020Article
- Multiple roles of HOX proteins in Metastasis: Let me count the ways.Cancer metastasis reviews · 2020Review
- Candidate methylation sites associated with endocrine therapy resistance in ER+/HER2- breast cancer.BMC cancer · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 4 institutions in 3 countries.
Funding
Abstract
Resistance to aromatase inhibitors (AIs) is a major clinical problem in the treatment of estrogen receptor (ER)-positive breast cancer. In two breast cancer cell line models of AI resistance, we identified widespread DNA hyper- and hypomethylation, with enrichment for promoter hypermethylation of developmental genes. For the homeobox gene HOXC10, methylation occurred in a CpG shore, which overlapped with a functional ER binding site, causing repression of HOXC10 expression. Although short-term blockade of ER signaling caused relief of HOXC10 repression in both cell lines and breast tumors, it also resulted in concurrent recruitment of EZH2 and increased H3K27me3, ultimately transitioning to increased DNA methylation and silencing of HOXC10. Reduced HOXC10 in vitro and in xenografts resulted in decreased apoptosis and caused antiestrogen resistance. Supporting this, we used paired primary and metastatic breast cancer specimens to show that HOXC10 was reduced in tumors that recurred during AI treatment. We propose a model in which estrogen represses apoptotic and growth-inhibitory genes such as HOXC10, contributing to tumor survival, whereas AIs induce these genes to cause apoptosis and therapeutic benefit, but long-term AI treatment results in permanent repression of these genes via methylation and confers resistance. Therapies aimed at inhibiting AI-induced histone and DNA methylation may be beneficial in blocking or delaying AI resistance.
Indexed as
Identifiers
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.