@article{d977817b938f4f42928bc9c65d50d14d,
title = "PLK1 stabilizes a MYC-dependent kinase network in aggressive B cell lymphomas",
abstract = "Concordant activation of MYC and BCL-2 oncoproteins in double-hit lymphoma (DHL) results in aggressive disease that is refractory to treatment. By integrating activity-based proteomic profiling and drug screens, polo-like kinase-1 (PLK1) was identified as an essential regulator of the MYC-dependent kinome in DHL. Notably, PLK1 was expressed at high levels in DHL, correlated with MYC expression, and connoted poor outcome. Further, PLK1 signaling augmented MYC protein stability, and in turn, MYC directly induced PLK1 transcription, establishing a feed-forward MYC-PLK1 circuit in DHL. Finally, inhibition of PLK1 triggered degradation of MYC and of the antiapoptotic protein MCL-1, and PLK1 inhibitors showed synergy with BCL-2 antagonists in blocking DHL cell growth, survival, and tumorigenicity, supporting clinical targeting of PLK1 in DHL.",
author = "Yuan Ren and Chengfeng Bi and Xiaohong Zhao and Tint Lwin and Cheng Wang and Ji Yuan and Silva, {Ariosto S.} and Shah, {Bijal D.} and Bin Fang and Tao Li and Koomen, {John M.} and Huijuan Jiang and Chavez, {Julio C.} and Pham, {Lan V.} and Sudalagunta, {Praneeth R.} and Lixin Wan and Xuefeng Wang and Dalton, {William S.} and Moscinski, {Lynn C.} and Shain, {Kenneth H.} and Julie Vose and Cleveland, {John L.} and Sotomayor, {Eduardo M.} and Kai Fu and Jianguo Tao",
note = "Funding Information: We sincerely thank Yuzhuo Wang for providing the DEL PDX model (38). We are also grateful for expert technical support from members of the Tao, Fu, Cleveland, Koomen, Silva, and Shain laboratories for their input, and the Proteomics and Metabolomics, Molecular Genomics, Translational Research, Flow Cytometry, and Biostatistics and Bioinformatics Cores of the Moffitt Cancer Center for outstanding service. This work was supported in part by grants from the National Cancer Institute (NCI) (CA179062, CA134807, and CA137123 to JT and EMS), a grant from the Lymphoma Research Foundation (to KF), a sponsored research agreement from Incyte Corp. (to JT), the Nebraska Department of Health (LB506-18-22 to KF), NCI Cancer Center support grants (P30-CA036727 and P30-CA076292), the Cortner-Couch Chair for Cancer Research from the University of South Florida School of Medicine (to JLC), Lesa France Kennedy (to JLC), the Pentecost Personalized Research Foundation (to ASS and KHS), the H. Lee Moffitt Cancer Center Physical Sciences in Oncology (PSOC) grant (1U54CA193489-01A1), and funds from the state of Florida to the Moffitt Cancer Center and Research Institute. Access to primary DHL patient specimens was made possible through the Total Cancer Care Protocol at the Moffitt Cancer Center.",
year = "2018",
month = dec,
day = "3",
doi = "10.1172/JCI122533",
language = "English (US)",
volume = "128",
pages = "5531--5548",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "12",
}