Open AccessIdentification of proteasomal catalytic subunit PSMA 6 as a therapeutic target for lung cancer
Author(s) -
Kakumu Tomohiko,
Sato Mitsuo,
Goto Daiki,
Kato Toshio,
Yogo Naoyuki,
Hase Tetsunari,
Morise Masahiro,
Fukui Takayuki,
Yokoi Kohei,
Sekido Yoshitaka,
Girard Luc,
Minna John D.,
Byers Lauren A.,
Heymach John V.,
Coombes Kevin R.,
Kondo Masashi,
Hasegawa Yoshinori
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13185
Subject(s) - spliceosome , cancer research , biology , gene silencing , cell cycle , lung cancer , gene , cancer , proteasome , microbiology and biotechnology , rna , genetics , medicine , pathology , rna splicing
To identify potential therapeutic targets for lung cancer, we performed semi‐genome‐wide sh RNA screening combined with the utilization of genome‐wide expression and copy number data. sh RNA 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 PSMA 6 , 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 PSMA 6 in lung cancer. Silencing of PSMA 6 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 PSMA 6 serves as an attractive target with a high therapeutic index for lung cancer.