ArticleOncogene2017
Retinoic acid directs breast cancer cell state changes through regulation of TET2-PKCζ pathway.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 36 papers.
What it found
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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.
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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
36 citing papers in PubMed, 49 citations in OpenAlex.
- Engineered pluronic nanomicelles containing ATRA and sodium butyrate for selective TNBC differentiation therapy.Medical oncology (Northwood, London, England) · 2025Article
- TET-mediated 5hmC in breast cancer: mechanism and clinical potential.Epigenetics · 2025Review
- Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation.Cell reports · 2025Article
- Control of epithelial homeostasis by apical polarity: it takes a network.Biochemical Society transactions · 2025Article
- High Expression ofCancer genomics & proteomics · 2025Article
- RNA modification gene WDR4 facilitates tumor progression and immunotherapy resistance in breast cancer.Journal of advanced research · 2025Article
- Review
- Vitamin C enhances co-localization of novel TET1 nuclear bodies with both Cajal and PML bodies in colorectal cancer cells.Epigenetics · 2024Article
- Perturbation of mammary epithelial cell apicobasal polarity by RHBDF1-facilitated nuclear translocation of PKCζ.Biological research · 2024Article
- Selective Estrogen Receptor Modulators' (SERMs) Influence onInternational journal of molecular sciences · 2024Article
- Human esophageal cancer stem-like cells escape the cytotoxicity of natural killer cells via down-regulation of ULBP-1.Journal of translational medicine · 2024Article
- Micronutrient regulation of the DNA methylome.Frontiers in epigenetics and epigenomics · 2024Review
- TET Enzymes and 5hmC Levels in Carcinogenesis and Progression of Breast Cancer: Potential Therapeutic Targets.International journal of molecular sciences · 2023Review
- Structural requirement of RARγ agonism through computational aspects.Journal of molecular modeling · 2023Article
- Nanomedicine strategies to counteract cancer stemness and chemoresistance.Exploration of targeted anti-tumor therapy · 2023Review
- Tumour suppressor TET2 safeguards enhancers from aberrant DNA methylation and epigenetic reprogramming in ERα-positive breast cancer cells.Epigenetics · 2022Article
- DysregulatedCancers · 2021Review
- Non-Coding RNAs in Retinoic Acid as Differentiation and Disease Drivers.Non-coding RNA · 2021Review
- Breast cancer stem cells: A review of their characteristics and the agents that affect them.Molecular carcinogenesis · 2021Review
- Protein Kinase C Alpha (PKCα) overexpression leads to a better response to retinoid acid therapy through Retinoic Acid Receptor Beta (RARβ) activation in mammary cancer cells.Journal of cancer research and clinical oncology · 2020Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The key molecular mechanism governing the cancer cell state (stem cell-like state vs differentiation state) to control the cancer stem cell (CSC) pool remains elusive. This study provides the first evidence showing that all-trans retinoic acid (ATRA) induces the interaction and chromatin recruitment of a novel RARβ-TET2 complex to epigenetically activate a specific cohort of gene targets, including MiR-200c. TET2-activated miR-200c further targets and suppresses PKCζ, a cell polarity protein that has a pivotal role in directing asymmetric division of mammalian stem cells to sustain the stem cell pool. Our data reveal that pharmacological concentration of ATRA effectively downregulates PKCζ through activation of miR-200c, leading to a decrease of the stem cell-like populations from non-tumorigenic mammary epithelial cells and non-aggressive breast cancer cells. However, aggressive breast cancer cells that manifest TET2-miR-200c dysregulation sustain a CSC pool highly resistant to ATRA, where inhibition of PKCζ directs the resistant CSCs to the luminal cell-like state and sensitization to tamoxifen, resulting in abrogation of mammary tumor growth and progression. Together, these findings elucidate a novel RARβ-TET2-miR-200c-PKCζ signaling pathway that directs cancer cell state changes and also provide previously unidentified therapeutic implications for PKCζ inhibitors in diminishment of breast CSCs to eradicate breast cancer.
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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.