RRC ID 49633
Author Kakumu T, Sato M, Goto D, Kato T, Yogo N, Hase T, Morise M, Fukui T, Yokoi K, Sekido Y, Girard L, Minna JD, Byers LA, Heymach JV, Coombes KR, Kondo M, Hasegawa Y.
Title Identification of proteasomal catalytic subunit PSMA6 as a therapeutic target for lung cancer.
Journal Cancer Sci.
Abstract To identify potential therapeutic targets for lung cancer, we performed semi-genome-wide shRNA screening combined with the utilization of genome-wide expression and copy number data. shRNA screening targeting 5043 genes in NCI-H460 identified 51 genes as candidates. Pathway analysis revealed that the 51 genes were enriched for the five pathways, including ribosome, proteasome, RNA polymerase, pyrimidine metabolism and spliceosome pathways. We focused on the proteasome pathway that involved six candidate genes because its activation has been demonstrated in diverse human malignancies, including lung cancer. Microarray expression and array CGH data showed that PSMA6, a proteasomal subunit of a 20S catalytic core complex, was highly expressed in lung cancer cell lines, with recurrent gene amplifications in some cases. Therefore, we further examined the roles of PSMA6 in lung cancer. Silencing of PSMA6 induced apoptosis or G2/M cell cycle arrest in cancer cell lines but not in an immortalized normal lung cell line. These results suggested that PSMA6 serves as an attractive target with a high therapeutic index for lung cancer.
Volume 108(4)
Pages 732-743
Published 2017-4
DOI 10.1111/cas.13185
PMID 28165654
PMC PMC5406588
MeSH A549 Cells Aged Apoptosis / genetics Blotting, Western Carcinoma, Non-Small-Cell Lung / genetics* Carcinoma, Non-Small-Cell Lung / metabolism Carcinoma, Non-Small-Cell Lung / pathology Catalytic Domain / genetics* Cell Line Cell Line, Tumor Cell Proliferation / genetics Cell Survival / genetics Female G2 Phase Cell Cycle Checkpoints / genetics Gene Amplification Gene Expression Profiling / methods Gene Expression Regulation, Neoplastic* Humans Immunohistochemistry Kaplan-Meier Estimate Lung Neoplasms / genetics* Lung Neoplasms / metabolism Lung Neoplasms / pathology Male Molecular Targeted Therapy Proteasome Endopeptidase Complex / genetics* Proteasome Endopeptidase Complex / metabolism RNA Interference Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / genetics
IF 4.751
DNA material pLenti6-PSMA6 (RDB15486)