The Oncogenic STP Axis Promotes Triple-Negative Breast Cancer via Degradation of the REST Tumor Suppressor

• DOI: 10.1016/j.celrep.2014.10.011
• Publication Date: 2014-11-06T18:52:16Z
• Authors: Kristen L. Karlin; Gourish Mondal; Jessica K. Hartman; Siddhartha Tyagi; Sarah J. Kurley; Chris S. Bland; Tiffany Y.T. Hsu; Alexander Renwick; Justin E. Fang; Ilenia Migliaccio; Celetta Callaway; Amritha Nair; Rocio Dominguez-V...; Don X. Nguyen; C. Kent Osborne; Rachel Schiff; Li-Yuan Yu-Lee; Sung Y. Jung; Dean P. Edwards; Susan G. Hilsenbeck; Jeffrey M. Rosen; Xiang H.-F. Zhang; Chad A. Shaw; Fergus J. Couch; Thomas F. Westbrook
• Keywords: Triple-negative breast cancer; Rest (music); Degron

Defining the molecular networks that drive breast cancer has led to therapeutic interventions and improved patient survival. However, aggressive triple-negative subtype (TNBC) remains recalcitrant targeted therapies because its etiology is poorly defined. In this study, we used a forward genetic screen discover an oncogenic network driving human TNBC. SCYL1, TEX14, PLK1 ("STP axis") cooperatively trigger degradation of REST tumor suppressor protein, frequent event in The STP axis induces by phosphorylating conserved phospho-degron bridging interaction with ubiquitin-ligase βTRCP. Inhibition leads increased protein levels impairs TNBC transformation, progression, metastasis. Expression correlates low TNBCs poor clinical outcome for patients. Our findings demonstrate STP-REST driver