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. 2022 Jun 8;12:797453. doi: 10.3389/fonc.2022.797453

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Copyright © 2022 Marvin, Spaans, de Kroon, Slieker, Khelil, ten Dijke, Ritsma and Jordanova

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Summary of the presented findings of TGF-β pathway, TGF-β regulator and TGF-β target proteins in AC, and differences in expression between AC and SCC in regard to these proteins. TGF-β pathway starts with binding of TGF-β to TβR2, leading to phosphorylation of TβR1 and subsequent phosphorylation of SMAD2. SMAD2 together with SMAD4 and SMAD3 (not indicated) form a complex and translocate to the nucleus to regulate transcription of TGF-β target genes PAI-1, αv integrin, β6 integrin, MMP2 and MMP9. Avβ6 integrin and MMP2/9 mediate cleavage of latent TGF-β. Hazard ratios (HR) are calculated low over high, and are shown for the proteins investigated in the present study. HRs are shown as RFS/DSS, significance (p ≤ 0.05) is indicated with*.