| Literature DB >> 27132469 |
Xing-Ding Zhang1, Veerabhadran Baladandayuthapani2, Heather Lin2, George Mulligan3, Bin Li3, Dixie-Lee W Esseltine3, Lin Qi4, Jianliang Xu5, Walter Hunziker5, Bart Barlogie6, Saad Z Usmani7, Qing Zhang7, John Crowley8, Antje Hoering8, Jatin J Shah9, Donna M Weber9, Elisabet E Manasanch9, Sheeba K Thomas9, Bing-Zong Li9, Hui-Han Wang9, Jiexin Zhang2, Isere Kuiatse9, Jin-Le Tang10, Hua Wang9, Jin He9, Jing Yang9, Enrico Milan11, Simone Cenci11, Wen-Cai Ma9, Zhi-Qiang Wang9, Richard Eric Davis9, Lin Yang12, Robert Z Orlowski13.
Abstract
Proteasome inhibitors have revolutionized outcomes in multiple myeloma, but they are used empirically, and primary and secondary resistance are emerging problems. We have identified TJP1 as a determinant of plasma cell proteasome inhibitor susceptibility. TJP1 suppressed expression of the catalytically active immunoproteasome subunits LMP7 and LMP2, decreased proteasome activity, and enhanced proteasome inhibitor sensitivity in vitro and in vivo. This occurred through TJP1-mediated suppression of EGFR/JAK1/STAT3 signaling, which modulated LMP7 and LMP2 levels. In the clinic, high TJP1 expression in patient myeloma cells was associated with a significantly higher likelihood of responding to bortezomib and a longer response duration, supporting the use of TJP1 as a biomarker to identify patients most likely to benefit from proteasome inhibitors.Entities:
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Year: 2016 PMID： 27132469 PMCID： PMC4983190 DOI： 10.1016/j.ccell.2016.03.026
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743