Impaired AKT signaling and lung tumorigenesis by PIERCE1 ablation in KRAS-mutant non-small cell lung cancer

Jae il Roh, Jaehoon Lee, Young Hoon Sung, Jahyun Oh, Do Young Hyeon, Yujin Kim, Seungeon Lee, Sushil Devkota, Hye Jeong Kim, Bomin Park, Taewook Nam, Yaechan Song, Yonghwan Kim, Daehee Hwang, Han Woong Lee

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6 Citations (Scopus)


KRAS-mutant non-small cell lung cancer (NSCLC) is a major lung cancer subtype that leads to many cancer-related deaths worldwide. Although numerous studies on KRAS-mutant type NSCLC have been conducted, new oncogenic or tumor suppressive genes need to be detected because a large proportion of NSCLC patients does not respond to currently used therapeutics. Here, we show the tumor-promoting function of a cell cycle-related protein, PIERCE1, in KRAS-mutant NSCLC. Mechanistically, PIERCE1 depletion inhibits cell growth and AKT phosphorylation (pAKT) at S473, which is particularly observed in KRAS-mutant lung cancers. Analyses of AKT-related genes using microarray, immunoblotting, and real-time quantitative PCR indicated that PIERCE1 negatively regulates the gene expression of the AKT suppressor, TRIB3, through the CHOP pathway, which is a key regulatory pathway for TRIB3 expression. Similarly, in vivo analyses of PIERCE1 depletion in the KRAS mutation-related lung cancer mouse models revealed the suppressive effect of PIERCE1 knockout in urethane- and KRASG12D-induced lung tumorigenesis with decreased pAKT levels observed in the tumors. Tissue microarrays of human lung cancers indicated the expression of PIERCE1 in 83% of lung cancers and its correlation with pAKT expression. Thus, we illustrate how PIERCE1 depletion may serve as a therapeutic strategy against KRAS-mutant NSCLC and propose the clinical benefit of PIERCE1.

Original languageEnglish
Pages (from-to)5876-5887
Number of pages12
Issue number36
Publication statusPublished - 2020 Sept 3

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research


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