@article{88051,
  keywords = {Animals, Protein Structure, Tertiary, Humans, phosphorylation, Transcription Factors, Mice, Female, Cell Line, Tumor, Breast Neoplasms, Lung Neoplasms, Epithelial-Mesenchymal Transition, Proteolysis, Mice, Inbred BALB C, TRPP Cation Channels, Snail Family Transcription Factors, Mice, Nude, Neoplasm Transplantation, Disease-Free Survival, F-Box Proteins, Kaplan-Meier Estimate, Protein-Arginine N-Methyltransferases, SKP Cullin F-Box Protein Ligases, Ubiquitination},
  author = {Hanqiu Zheng and Minhong Shen and Yin-Lian Zha and Wenyang Li and Yong Wei and Mario Andres Blanco and Guangwen Ren and Tianhua Zhou and Peter Storz and Hui-Yun Wang and Yibin Kang},
  title = {PKD1 phosphorylation-dependent degradation of SNAIL by SCF-FBXO11 regulates epithelial-mesenchymal transition and metastasis.},
  abstract = {<p>Metastatic dissemination is often initiated by the reactivation of an embryonic development program referred to as epithelial-mesenchymal transition (EMT). The transcription factor SNAIL promotes EMT and elicits associated pathological characteristics such as invasion, metastasis, and stemness. To better understand the posttranslational regulation of SNAIL, we performed a luciferase-based, genome-wide E3 ligase siRNA library screen and identified SCF-FBXO11 as an important E3 that targets SNAIL for ubiquitylation and degradation. Furthermore, we discovered that SNAIL degradation by FBXO11 is dependent on Ser-11 phosphorylation of SNAIL by protein kinase D1 (PKD1). FBXO11 blocks SNAIL-induced EMT, tumor initiation, and metastasis in multiple breast cancer models. These findings establish the PKD1-FBXO11-SNAIL axis as a mechanism of posttranslational regulation of EMT and cancer metastasis.</p>
},
  year = {2014},
  journal = {Cancer Cell},
  volume = {26},
  pages = {358-73},
  month = {09/2014},
  issn = {1878-3686},
  doi = {10.1016/j.ccr.2014.07.022},
  language = {eng},
}