@article{6c77dd92cd434132ba2df417e4008a1a,
title = "The Oncogenic STP Axis Promotes Triple-Negative Breast Cancer via Degradation of the REST Tumor Suppressor",
abstract = "Defining the molecular networks that drive breast cancer has led to therapeutic interventions and improved patient survival. However, the aggressive triple-negative breast cancer subtype (TNBC) remains recalcitrant to targeted therapies because its molecular etiology is poorly defined. In this study, we used a forward genetic screen to discover an oncogenic network driving human TNBC. SCYL1, TEX14, and PLK1 ({"}STP axis{"}) cooperatively trigger degradation of the REST tumor suppressor protein, a frequent event in human TNBC. The STP axis induces REST degradation by phosphorylating a conserved REST phospho-degron and bridging REST interaction with the ubiquitin-ligase βTRCP. Inhibition of the STP axis leads to increased REST protein levels and impairs TNBC transformation, tumor progression, and metastasis. Expression of the STP axis correlates with low REST protein levels in human TNBCs and poor clinical outcome for TNBC patients. Our findings demonstrate that the STP-REST axis is a molecular driver of human TNBC.",
author = "Karlin, {Kristen L.} and Gourish Mondal and Hartman, {Jessica K.} and Siddhartha Tyagi and Kurley, {Sarah J.} and Bland, {Chris S.} and Hsu, {Tiffany Y.T.} and Alexander Renwick and Fang, {Justin E.} and Ilenia Migliaccio and Celetta Callaway and Amritha Nair and Rocio Dominguez-Vidana and Nguyen, {Don X.} and Osborne, {C. Kent} and Rachel Schiff and Yu-Lee, {Li Yuan} and Jung, {Sung Y.} and Edwards, {Dean P.} and Hilsenbeck, {Susan G.} and Rosen, {Jeffrey M.} and Zhang, {Xiang H.F.} and Shaw, {Chad A.} and Couch, {Fergus J.} and Westbrook, {Thomas F.}",
note = "Funding Information: We would like to thank members of the T.F.W., F.J.C., and C.A.S. laboratories for helpful comments. The authors also acknowledge the joint participation by Adrienne Helis Melvin Medical Research Foundation through its direct engagement in the continuous active conduct of medical research in conjunction with Baylor College of Medicine for cancer research. The Dan L. Duncan Cancer Center Shared Resources was supported by the NCI P30CA125123 Center Grant and provided technical assistance including Cell-Based Assay Screening Service (Dan Liu), Genomic and RNA Profiling Resource (Lisa White), Biostatistics & Informatics Shared Resource (S.G.H.), and Cytometry and Cell Sorting (Joel Sederstrom). Authors would like to acknowledge Nexcelom for providing support for Celigo image data management system. Research at Mayo Clinic was supported by the Breast Cancer Research Foundation (BCRF), NIH Grant CA116167, an NCI specialized program of research excellence (SPORE) in Breast Cancer (P50 CA166201), the David and Margaret T. Grohne Family Foundation, and the Ting Tsung and Wei Fong Chao Foundation. K.L.K. was supported by DOD predoctoral fellowship (BC094077) and NIH training grant (5 T32 GM008231). T.F.W. was supported by CPRIT (RP120583), the Susan G. Komen for the Cure (KG090355), the NIH (1R01CA178039-01), and the DOD Breast Cancer Research Program (BC120604). ",
year = "2014",
month = nov,
day = "20",
doi = "10.1016/j.celrep.2014.10.011",
language = "English (US)",
volume = "9",
pages = "1318--1332",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "4",
}