ArticleCell research2020
The Msi1-mTOR pathway drives the pathogenesis of mammary and extramammary Paget's disease.
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Article in Cell research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28 citing papers in PubMed, 68 citations in OpenAlex.
- Treatment of extramammary Paget's disease with sirolimus: A case series.JAAD case reports · 2026Article
- Identification of two genes associated with recurrence in Paget's disease and construction of a predictive model.Frontiers in genetics · 2026Article
- Plus-strand RNA viruses hijack Musashi homolog 1 to shield viral RNA from cytoplasmic ribonuclease degradation.Journal of virology · 2025Article
- Insights Into Mammary and Extramammary Paget's Disease: Diagnosis, Management, and Recent Advances.Cureus · 2025Review
- Identification of FSH-regulated and estrous stage-specific transcriptional networks in mouse ovaries.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Paget's Disease of the Male Breast: A Diagnostic Challenge.Acta dermato-venereologica · 2025Article
- Insights into early acne pathogenesis: Exploring intercellular dynamics and key dysregulated genes.Cell signaling · 2025Article
- Advancements in the Application of scRNA-Seq in Breast Research: A Review.International journal of molecular sciences · 2024Review
- Immunotherapy may be more appropriate for ERBB2 low-expressing extramammary paget's disease patients: a prognosis analysis and exploration of targeted therapy and immunotherapy of extramammary paget's disease patients.Cancer immunology, immunotherapy : CII · 2024Article
- Construction and verification of an innovative immune-related and hallmark gene sets prognostic model for bladder cancer.Translational cancer research · 2024Article
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- Analysis of intracellular communication reveals consistent gene changes associated with early-stage acne skin.Cell communication and signaling : CCS · 2024Article
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- Therapeutic Approaches for Non-Melanoma Skin Cancer: Standard of Care and Emerging Modalities.International journal of molecular sciences · 2024Review
- Analysis of Intracellular Communication Reveals Consistent Gene Changes Associated with Early-Stage Acne Skin.Research square · 2024Article
- Unraveling the landscape of non-melanoma skin cancer through single-cell RNA sequencing technology.Frontiers in oncology · 2024Review
- Untargeted metabolomics yields insight into extramammary Paget's disease mechanisms.Frontiers in oncology · 2024Article
- A Single-Cell Atlas of an Early Mongolian Sheep Embryo.Veterinary sciences · 2023Article
- Correlation analysis between androgen receptor and the clinicopathological features and prognosis of mammary Paget's disease.Journal of cancer research and clinical oncology · 2023Article
- Combined analyses of RNA-sequence and Hi-C along with GWAS loci-A novel approach to dissect keloid disorder genetic mechanism.PLoS genetics · 2022Article
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Authors and funding
31 authors at 10 institutions in 2 countries.
Yongli Song *State Key Laboratories for Agrobiotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Christian F Guerrero-Juarez *Department of Mathematics, NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, CA, 92697, USA.ORCID http://orcid.org/0000-0002-6245-6412
Zhongjian Chen *Shanghai Skin Disease Hospital, Shanghai, 200443, China.
Yichen TangShanghai Skin Disease Hospital, Shanghai, 200443, China.
Xianghui MaState Key Laboratories for Agrobiotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Cong LvState Key Laboratories for Agrobiotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Xueyun BiState Key Laboratories for Agrobiotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Min DengState Key Laboratories for Agrobiotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Lina BuState Key Laboratories for Agrobiotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Yuhua TianState Key Laboratories for Agrobiotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Ruiqi LiuState Key Laboratories for Agrobiotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Ran ZhaoState Key Laboratories for Agrobiotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Jiuzhi XuState Key Laboratories for Agrobiotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Xiaole ShengState Key Laboratories for Agrobiotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Sujuan DuState Key Laboratories for Agrobiotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Yeqiang LiuShanghai Skin Disease Hospital, Shanghai, 200443, China.
Yunlu ZhuShanghai Skin Disease Hospital, Shanghai, 200443, China.
Shi-Jun ShanDepartment of Dermatology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361005, China.
Hong-Duo ChenDepartment of Dermatology, No.1 Hospital of China Medical University, Shenyang, Liaoning, 110001, China.
Yiqiang ZhaoState Key Laboratories for Agrobiotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Guangbiao ZhouState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.ORCID http://orcid.org/0000-0002-6327-2316
Jianwei ShuaiDepartment of Physics and State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, Xiamen University, Xiamen, Fujian, 361005, China.
Fazheng RenBeijing Advanced Innovation Center for Food Nutrition and Human Health and, College of Food Sciences and Nutritional Engineering, China Agricultural University, Beijing, 100193, China.
Lixiang XueMedical Research Center, Department of Radiation Oncology, Peking University Third Hospital, Beijing, 100191, China.
Zhaoxia YingThe Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China.
Xing DaiDepartments of Biological Chemistry and Dermatology, School of Medicine, University of California, Irvine, CA, 92697, USA.
Christopher J LengnerDepartment of Animal Biology, School of Veterinary Medicine, and Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, 19082, USA.
Bogi AndersenDepartments of Medicine and Biological Chemistry, University of California, Irvine, CA, 92697, USA.
Maksim V PlikusDepartment of Developmental and Cell Biology, Sue and Bill Gross Stem Cell Research, Center for Complex Biological Systems, University of California, Irvine, CA, 92697, USA.ORCID http://orcid.org/0000-0002-8845-2559
Qing NieDepartment of Mathematics, NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, CA, 92697, USA.
Zhengquan YuState Key Laboratories for Agrobiotechnology and Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Biological Sciences, China Agricultural University, Beijing, 100193, China. zyu@cau.edu.cn.ORCID http://orcid.org/0000-0001-8696-2013
China Agricultural University · CNUniversity of California, Irvine · USShanghai Skin Disease Hospital · CNXiamen University · CNCalifornia Institute for Regenerative Medicine · USChina Medical University · CNChinese Academy of Medical Sciences & Peking Union Medical College · CNJilin Province Science and Technology Department · CNPeking University · CNSecond Affiliated Hospital of Xi'an Jiaotong University · CN
Funding
University of California Health Participation in the National COVID Cohort Collaborative (N3C)UL1TR001414 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI COOPER, DAN M, VILAIN, ERIC J. · 2015 to 2023
$35.1MShared Resource Core: Single Cell AnalysisU54CA217378 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI LANDER, ARTHUR D · 2018 to 2022
$9.7MTranscriptional Co-Regulators in EpidermisR01AR044882 · NIAMS · UNIVERSITY OF CALIFORNIA SAN DIEGO · PI Bogi Andersen · 1998 to 2026
$9.0MUCI P30 Skin Center Systems Biology CoreP30AR075047 · NIAMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI ANDERSEN, BOGI, GANESAN, ANAND K · 2019 to 2025
$5.1MMultiscale Models of Wound Cell Plasticity for RegenerationU01AR073159 · NIAMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI DAI, XING, NIE, QING · 2018 to 2022
$3.5MInduction of fat regeneration in skin wounds by hair follicle signalingR01AR067273 · NIAMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI PLIKUS, MAKSIM V · 2014 to 2018
$1.9MSkin Defense by Dermal AdipocytesR01AR069653 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GALLO, RICHARD L · 2016 to 2020
$1.9MHoward Hughes Medical InstituteNCATS NIH HHS UL1 TR001414NCI NIH HHS U54 CA217378NIAMS NIH HHS P30 AR075047NIAMS NIH HHS R01 AR044882NIAMS NIH HHS R01 AR067273NIAMS NIH HHS R01 AR069653NIAMS NIH HHS U01 AR073159
Abstract
Mammary and extramammary Paget's Diseases (PD) are a malignant skin cancer characterized by the appearance of Paget cells. Although easily diagnosed, its pathogenesis remains unknown. Here, single-cell RNA-sequencing identified distinct cellular states, novel biomarkers, and signaling pathways - including mTOR, associated with extramammary PD. Interestingly, we identified MSI1 ectopic overexpression in basal epithelial cells of human PD skin, and show that Msi1 overexpression in the epidermal basal layer of mice phenocopies human PD at histopathological, single-cell and molecular levels. Using this mouse model, we identified novel biomarkers of Paget-like cells that translated to human Paget cells. Furthermore, single-cell trajectory, RNA velocity and lineage-tracing analyses revealed a putative keratinocyte-to-Paget-like cell conversion, supporting the in situ transformation theory of disease pathogenesis. Mechanistically, the Msi1-mTOR pathway drives keratinocyte-Paget-like cell conversion, and suppression of mTOR signaling with Rapamycin significantly rescued the Paget-like phenotype in Msi1-overexpressing transgenic mice. Topical Rapamycin treatment improved extramammary PD-associated symptoms in humans, suggesting mTOR inhibition as a novel therapeutic treatment in PD.
Indexed as
AdultAgedAnimalsAntibiotics, AntineoplasticBiomarkersBreast NeoplasmsFemaleHumansMaleMiceMiddle AgedNerve Tissue ProteinsPaget Disease, ExtramammaryRNA-Binding ProteinsSirolimusTOR Serine-Threonine KinasesAntibiotics, AntineoplasticBiomarkersMsi1h protein, mouseMSI1 protein, humanMTOR protein, humanNerve Tissue ProteinsRNA-Binding ProteinsSirolimusTOR Serine-Threonine Kinases
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