Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

Distinct mechanisms of TGF-β1–mediated epithelial-to-mesenchymal transition and metastasis during skin carcinogenesis
Gangwen Han, … , Molly Kulesz-Martin, Xiao-Jing Wang
Gangwen Han, … , Molly Kulesz-Martin, Xiao-Jing Wang
Published July 1, 2005
Citation Information: J Clin Invest. 2005;115(7):1714-1723. https://doi.org/10.1172/JCI24399.
View: Text | PDF
Research Article Oncology Article has an altmetric score of 6

Distinct mechanisms of TGF-β1–mediated epithelial-to-mesenchymal transition and metastasis during skin carcinogenesis

  • Text
  • PDF
Abstract

In the present study, we demonstrated that human skin cancers frequently overexpress TGF-β1 but exhibit decreased expression of the TGF-β type II receptor (TGF-βRII). To understand how this combination affects cancer prognosis, we generated a transgenic mouse model that allowed inducible expression of TGF-β1 in keratinocytes expressing a dominant negative TGF-βRII (ΔβRII) in the epidermis. Without ΔβRII expression, TGF-β1 transgene induction in late-stage, chemically induced papillomas failed to inhibit tumor growth but increased metastasis and epithelial-to-mesenchymal transition (EMT), i.e., formation of spindle cell carcinomas. Interestingly, ΔβRII expression abrogated TGF-β1–mediated EMT and was accompanied by restoration of membrane-associated E-cadherin/catenin complex in TGF-β1/ΔβRII compound tumors. Furthermore, expression of molecules thought to mediate TGF-β1–induced EMT was attenuated in TGF-β1/ΔβRII–transgenic tumors. However, TGF-β1/ΔβRII–transgenic tumors progressed to metastasis without losing expression of the membrane-associated E-cadherin/catenin complex and at a rate higher than those observed in nontransgenic, TGF-β1–transgenic, or ΔβRII-transgenic mice. Abrogation of Smad activation by ΔβRII correlated with the blockade of EMT. However, ΔβRII did not alter TGF-β1–mediated expression of RhoA/Rac and MAPK, which contributed to increased metastasis. Our study provides evidence that TGF-β1 induces EMT and invasion via distinct mechanisms. TGF-β1–mediated EMT requires functional TGF-βRII, whereas TGF-β1–mediated tumor invasion cooperates with reduced TGF-βRII signaling in tumor epithelia.

Authors

Gangwen Han, Shi-Long Lu, Allen G. Li, Wei He, Christopher L. Corless, Molly Kulesz-Martin, Xiao-Jing Wang

×

Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 Total
Citations: 1 1 1 3 7 4 3 4 4 5 8 6 5 12 3 9 10 6 7 2 101
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2015 (8)

Title and authors Publication Year
Asporin Is a Fibroblast-Derived TGF-β1 Inhibitor and a Tumor Suppressor Associated with Good Prognosis in Breast Cancer
P Maris, A Blomme, AP Palacios, B Costanza, A Bellahcène, E Bianchi, S Gofflot, P Drion, GE Trombino, ED Valentin, PG Cusumano, S Maweja, G Jerusalem, P Delvenne, E Lifrange, V Castronovo, A Turtoi, C Kemp
PLoS Medicine 2015
Repression of TIF1γ by SOX2 promotes TGF-β-induced epithelial–mesenchymal transition in non-small-cell lung cancer
L Wang, H Yang, Z Lei, J Zhao, Y Chen, P Chen, C Li, Y Zeng, Z Liu, X Liu, HT Zhang
Oncogene 2015
Targeted Therapy in Oropharyngeal Squamous Cell Carcinoma: The Implications of HPV for Therapy
A Hay, I Ganly
Rare Cancers and Therapy 2015
Extracellular acidity strengthens mesenchymal stem cells to promote melanoma progression
S Peppicelli, F Bianchini, A Toti, A Laurenzana, G Fibbi, L Calorini
Cell cycle (Georgetown, Tex.) 2015
Molecular Aspects of Head and Neck Cancer Therapy
SV Puram, JW Rocco
Hematology/Oncology Clinics of North America 2015
Epithelial-mesenchymal transition during extravillous trophoblast differentiation
JE Davies, J Pollheimer, HE Yong, MI Kokkinos, B Kalionis, M Knöfler, P Murthi
Cell adhesion & migration 2015
KLF8 promotes tumorigenesis, invasion and metastasis of colorectal cancer cells by transcriptional activation of FHL2
Q Yan, W Zhang, Y Wu, M Wu, M Zhang, X Shi, J Zhao, Q Nan, Y Cheng, L Wang, T Cheng, J Li, Y Bai, S Liu, J Wang
Oncotarget 2015
Loss of RAB1B promotes triple-negative breast cancer metastasis by activating TGF-β/SMAD signaling
HL Jiang, HF Sun, SP Gao, LD Li, X Hu, J Wu, W Jin
Oncotarget 2015

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Referenced in 3 patents
103 readers on Mendeley
See more details