ArticleCell reports2016
Control of Paneth Cell Fate, Intestinal Inflammation, and Tumorigenesis by PKCλ/ι.
Article in Cell reports, 2016. 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, 58 citations in OpenAlex.
- From inflammation to malignancy: the dynamic evolution of cancer-associated fibroblasts in IBD-CRC.Neoplasia (New York, N.Y.) · 2026Review
- 3D bioprinted human-scale intestine models for physiological and microbial insights through fluid-driven heterogeneity.Science advances · 2025Article
- Intestinal secretory differentiation reflects niche-driven phenotypic and epigenetic plasticity of a common signal-responsive terminal cell.Cell stem cell · 2025Article
- Cell polarity proteins promote macropinocytosis in response to metabolic stress.Nature communications · 2024Article
- Article
- Epithelial aPKC deficiency leads to stem cell loss preceding metaplasia in colorectal cancer initiation.Developmental cell · 2024Article
- Amino acid transporter SLC7A5 regulates cell proliferation and secretary cell differentiation and distribution in the mouse intestine.International journal of biological sciences · 2024Article
- Enhanced SREBP2-driven cholesterol biosynthesis by PKCλ/ι deficiency in intestinal epithelial cells promotes aggressive serrated tumorigenesis.Nature communications · 2023Article
- Potential Dietary and Therapeutic Strategies Involving Indole-3-Carbinole in Preclinical Models of Intestinal Inflammation.Nutrients · 2023Article
- General transcription factor TAF4 antagonizes epigenetic silencing by Polycomb to maintain intestine stem cell functions.Cell death and differentiation · 2023Article
- Hyaluronan driven by epithelial aPKC deficiency remodels the microenvironment and creates a vulnerability in mesenchymal colorectal cancer.Cancer cell · 2023Article
- Paneth cells as the cornerstones of intestinal and organismal health: a primer.EMBO molecular medicine · 2023Review
- Protein kinase Cλ/ι in cancer: a contextual balance of time and signals.Trends in cell biology · 2022Review
- PKCλ/ι inhibition activates an ULK2-mediated interferon response to repress tumorigenesis.Molecular cell · 2021Article
- Lonicerin targets EZH2 to alleviate ulcerative colitis by autophagy-mediated NLRP3 inflammasome inactivation.Acta pharmaceutica Sinica. B · 2021Article
- Article
- Noncanonical Functions of the Polycomb Group Protein EZH2 in Breast Cancer.The American journal of pathology · 2021Review
- EZH2 inhibitor GSK343 inhibits sepsis-induced intestinal disorders.Experimental and therapeutic medicine · 2021Article
- Review
- Stromal SOX2 Upregulation Promotes Tumorigenesis through the Generation of a SFRP1/2-Expressing Cancer-Associated Fibroblast Population.Developmental cell · 2021Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
Paneth cells are a highly specialized population of intestinal epithelial cells located in the crypt adjacent to Lgr5(+) stem cells, from which they differentiate through a process that requires downregulation of the Notch pathway. Their ability to store and release antimicrobial peptides protects the host from intestinal pathogens and controls intestinal inflammation. Here, we show that PKCλ/ι is required for Paneth cell differentiation at the level of Atoh1 and Gfi1, through the control of EZH2 stability by direct phosphorylation. The selective inactivation of PKCλ/ι in epithelial cells results in the loss of mature Paneth cells, increased apoptosis and inflammation, and enhanced tumorigenesis. Importantly, PKCλ/ι expression in human Paneth cells decreases with progression of Crohn's disease. Kaplan-Meier survival analysis of colorectal cancer (CRC) patients revealed that low PRKCI levels correlated with significantly worse patient survival rates. Therefore, PKCλ/ι is a negative regulator of intestinal inflammation and cancer through its role in Paneth cell homeostasis.
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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.