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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.
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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

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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

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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 2012 (12)

Title and authors Publication Year
The Molecular Pathogenesis of Head and Neck Squamous Cell Carcinoma
S. Michael Rothenberg, Leif Ellisen
Journal of Clinical Investigation 2012
Complex Regulation of the Pericellular Proteolytic Microenvironment during Tumor Progression and Wound Repair: Functional Interactions between the Serine Protease and Matrix Metalloproteinase Cascades
CE Wilkins-Port, SP Higgins, CE Higgins, I Kobori-Hotchkiss, PJ Higgins
Biochemistry Research International 2012
Complexities of TGF-β Targeted Cancer Therapy
EC Connolly, J Freimuth, RJ Akhurst
International journal of biological sciences 2012
The Dual Role of TGF in Human Cancer: From Tumor Suppression to Cancer Metastasis
JJ Lebrun
ISRN Molecular Biology 2012
Inhibition of dendritic cell migration by transforming growth factor-β1 increases tumor-draining lymph node metastasis
K Imai, Y Minamiya, S Koyota, M Ito, H Saito, Y Sato, S Motoyama, T Sugiyama, JI Ogawa
Journal of experimental & clinical cancer research : CR 2012
Spatiotemporal Regulation of Epithelial-Mesenchymal Transition Is Essential for Squamous Cell Carcinoma Metastasis
JH Tsai, JL Donaher, DA Murphy, S Chau, J Yang
Cancer Cell 2012
Crossing Paths in Human Renal Cell Carcinoma (hRCC)
GA Gallego, VM Villaamil, E Grande, IS Caínzos, LM Aparicio
International journal of molecular sciences 2012
The Role of TGFβ Signaling in Squamous Cell Cancer: Lessons from Mouse Models
AB Glick
Journal of Skin Cancer 2012
CD82 inhibits canonical Wnt signalling by controlling the cellular distribution of β-catenin in carcinoma cells
S Chigita, T Sugiura, M Abe, Y Kobayashi, M Shimoda, M Onoda, K Shirasuna
International journal of oncology 2012
Transforming growth factor-β enhances invasion and metastasis in Ras-transfected human malignant epidermal keratinocytes
M Davies, SS Prime, JW Eveson, N Price, A Ganapathy, A D'Mello, IC Paterson
International Journal of Experimental Pathology 2012
Loss of transforming growth factor beta type II receptor increases aggressive tumor behavior and reduces survival in lung adenocarcinoma and squamous cell carcinoma
SP Malkoski, SM Haeger, TG Cleaver, KJ Rodriguez, H Li, SL Lu, WJ Feser, AE Barón, D Merrick, JG Lighthall, H Ijichi, W Franklin, XJ Wang
Clinical cancer research 2012
Examination of Smad2 and Smad4 copy-number variations in skin cancers.
Shao Y, Zhang J, Zhang R, Wan J, Zhang W, Yu B
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 2012

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