Kruppel-like Transcription Factor KLF10 Suppresses TGF{beta}-Induced Epithelial-to-Mesenchymal Transition via a Negative Feedback Mechanism

In this study, we show how KLF10 opposes the prometastatic effects of TGFβ by limiting its ability to induce epithelial-to-mesenchymal transition (EMT). KLF10 depletion accentuated induction of EMT as assessed by multiple metrics. KLF10 occupied GC-rich sequences in the promoter region of the EMT-promoting transcription factor SLUG/SNAI2, repressing its transcription by recruiting HDAC1 and licensing the removal of activating histone acetylation marks. In clinical specimens of lung adenocarcinoma, low KLF10 expression associated with decreased patient survival, consistent with a pivotal role for KLF10 in distinguishing the antiproliferative versus prometastatic functions of TGFβ. Our results establish that KLF10 functions to suppress TGFβ-induced EMT, establishing a molecular basis for the dichotomy of TGFβ function during tumor progression. Cancer Res; 77(9); 2387–400. ©2017 AACR.

Source: Cancer Research - April 30, 2017 Category: Cancer & Oncology Authors: Vivek Kumar Mishra, Malayannan Subramaniam, Vijayalakshmi Kari, Kevin S. Pitel, Simon J. Baumgart, Ryan M. Naylor, Sankari Nagarajan, Florian Wegwitz, Volker Ellenrieder, John R. Hawse, Steven A. Johnsen Tags: Molecular and Cellular Pathobiology Source Type: research