| First Author | Mishra VK | Year | 2017 |
| Journal | Cancer Res | Volume | 77 |
| Issue | 9 | Pages | 2387-2400 |
| PubMed ID | 28249899 | Mgi Jnum | J:242170 |
| Mgi Id | MGI:5904570 | Doi | 10.1158/0008-5472.CAN-16-2589 |
| Citation | Mishra VK, et al. (2017) Kruppel-like Transcription Factor KLF10 Suppresses TGFbeta-Induced Epithelial-to-Mesenchymal Transition via a Negative Feedback Mechanism. Cancer Res 77(9):2387-2400 |
| abstractText | TGFbeta-SMAD signaling exerts a contextual effect that suppresses malignant growth early in epithelial tumorigenesis but promotes metastasis at later stages. Longstanding challenges in resolving this functional dichotomy may uncover new strategies to treat advanced carcinomas. The Kruppel-like transcription factor, KLF10, is a pivotal effector of TGFbeta/SMAD signaling that mediates antiproliferative effects of TGFbeta. In this study, we show how KLF10 opposes the prometastatic effects of TGFbeta 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 TGFbeta. Our results establish that KLF10 functions to suppress TGFbeta-induced EMT, establishing a molecular basis for the dichotomy of TGFbeta function during tumor progression. Cancer Res; 77(9); 2387-400. (c)2017 AACR. |
