Identification of proteasomal catalytic subunit PSMA6 as a therapeutic target for lung cancer

Tomohiko Kakumu, Mitsuo Sato, Daiki Goto, Toshio Kato, Naoyuki Yogo, Tetsunari Hase, Masahiro Morise, Takayuki Fukui, Kohei Yokoi, Yoshitaka Sekido, Luc Girard, John D. Minna, Lauren A. Byers, John V. Heymach, Kevin R. Coombes, Masashi Kondo, Yoshinori Hasegawa

Research output: Contribution to journalArticle

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)732-743
Number of pages12
JournalCancer Science
Volume108
Issue number4
DOIs
StatePublished - Apr 1 2017

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Keywords

  • Apoptosis
  • lung neoplasms
  • proteasome endopeptidase complex
  • small interfering RNA
  • spliceosomes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kakumu, T., Sato, M., Goto, D., Kato, T., Yogo, N., Hase, T., Morise, M., Fukui, T., Yokoi, K., Sekido, Y., Girard, L., Minna, J. D., Byers, L. A., Heymach, J. V., Coombes, K. R., Kondo, M., & Hasegawa, Y. (2017). Identification of proteasomal catalytic subunit PSMA6 as a therapeutic target for lung cancer. Cancer Science, 108(4), 732-743. https://doi.org/10.1111/cas.13185