有村 健
   Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine
   Position   Assistant Professor
Article types Original article
Language English
Peer review Non peer reviewed
Title Elucidating the role of EPPK1 in lung adenocarcinoma development.
Journal Formal name:BMC cancer
Abbreviation:BMC Cancer
ISSN code:14712407/14712407
Domestic / ForeginForegin
Volume, Issue, Page 24(1),pp.441
Author and coauthor Arimura Ken†, Kammer Michael, Rahman S M Jamshedur, Sheau-Chiann Chen, Zhao Shilin, Heidi Chen, Eisenberg Rosana, Zou Yong, Antic Sanja, Richmond Bradley, Tagaya Etsuko, Grogan Eric, Massion Pierre, Maldonado Fabien
Authorship Lead author
Publication date 2024/04
Summary BACKGROUND:We recently found that epiplakin 1 (EPPK1) alterations were present in 12% of lung adenocarcinoma (LUAD) cases and were associated with a poor prognosis in early-stage LUAD when combined with other molecular alterations. This study aimed to identify a probable crucial role for EPPK1 in cancer development.METHODS:EPPK1 mRNA and protein expression was analyzed with clinical variables. Normal bronchial epithelial cell lines were exposed to cigarette smoke for 16 weeks to determine whether EPPK1 protein expression was altered after exposure. Further, we used CRISPR-Cas9 to knock out (KO) EPPK1 in LUAD cell lines and observed how the cancer cells were altered functionally and genetically.RESULTS:EPPK1 protein expression was associated with smoking and poor prognosis in early-stage LUAD. Moreover, a consequential mesenchymal-to-epithelial transition was observed, subsequently resulting in diminished cell proliferation and invasion after EPPK1 KO. RNA sequencing revealed that EPPK1 KO induced downregulation of 11 oncogenes, 75 anti-apoptosis, and 22 angiogenesis genes while upregulating 8 tumor suppressors and 12 anti-cell growth genes. We also observed the downregulation of MYC and upregulation of p53 expression at both protein and RNA levels following EPPK1 KO. Gene ontology enrichment analysis of molecular functions highlighted the correlation of EPPK1 with the regulation of mesenchymal cell proliferation, mesenchymal differentiation, angiogenesis, and cell growth after EPPK1 KO.CONCLUSIONS:Our data suggest that EPPK1 is linked to smoking, epithelial to mesenchymal transition, and the regulation of cancer progression, indicating its potential as a therapeutic target for LUAD.
DOI 10.1186/s12885-024-12185-x
PMID 38594604