Cancers, Vol. 12, Pages 2864: Characterization of a PERK Kinase Inhibitor with Anti-Myeloma Activity
Cancers, Vol. 12, Pages 2864: Characterization of a PERK Kinase Inhibitor with Anti-Myeloma Activity
Cancers doi: 10.3390/cancers12102864
Authors:
Tina Bagratuni
Dimitrios Patseas
Nefeli Mavrianou-Koutsoukou
Christine Ivy Liacos
Aimilia D. Sklirou
Pantelis Rousakis
Maria Gavriatopoulou
Evangelos Terpos
Ourania E. Tsitsilonis
Ioannis P. Trougakos
Efstathios Kastritis
Meletios A. Dimopoulos
Due to increased immunoglobulin production and uncontrolled proliferation, multiple myeloma (MM) plasma cells develop a phenotype of deregulated unfolded protein response (UPR). The eIF2-alpha kinase 3 [EIF2αK3, protein kinase R (PKR)-like ER kinase (PERK)], the third known sensor of endoplasmic reticulum (ER) stress, is a serine-threonine kinase and, like the other two UPR-related proteins, i.e., IRE1 and ATF6, it is bound to the ER membrane. MM, like other tumors showing uncontrolled protein secretion, is highly dependent to UPR for survival; thus, inhibition of PERK can be an effective strategy to suppress growth of malignant plasma cells. Here, we have used GSK2606414, an ATP-competitive potent PERK inhibitor, and found significant anti-proliferative and apoptotic effects in a panel of MM cell lines. These effects were accompanied by the downregulation of key components of the PERK pathway as well as of other UPR elements. Consistently, PERK gene expression silencing significantly increased cell death in MM cells, highlighting the importance of...
Source: Cancers - Category: Cancer & Oncology Authors: Tina Bagratuni Dimitrios Patseas Nefeli Mavrianou-Koutsoukou Christine Ivy Liacos Aimilia D. Sklirou Pantelis Rousakis Maria Gavriatopoulou Evangelos Terpos Ourania E. Tsitsilonis Ioannis P. Trougakos Efstathios Kastritis Meletios A. Dimopoulos Tags: Article Source Type: research