Open AccessFAM111B enhances proliferation of KRAS ‐driven lung adenocarcinoma by degrading p16
Author(s) -
Kawasaki Keisuke,
Nojima Satoshi,
Hijiki Sachiko,
Tahara Shinichiro,
Ohshima Kenji,
Matsui Takahiro,
Hori Yumiko,
Kurashige Masako,
Umeda Daisuke,
Kiyokawa Hiroki,
Kido Kansuke,
Okuzaki Daisuke,
Morii Eiichi
Publication year - 2020
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.14483
Subject(s) - kras , adenocarcinoma , cyclin d1 , lung cancer , immunohistochemistry , cancer research , cell cycle , cancer , biology , tumor progression , lung , cell growth , cell cycle progression , cyclin , pathology , medicine , colorectal cancer , genetics
Lung cancer is a common type of cancer that represents a health problem worldwide; lung adenocarcinoma (LUAD) is a major subtype of lung cancer. Although several treatments for LUAD have been developed, the mortality rate remains high because of uncontrollable progression. Further biological and clinicopathological studies are therefore needed. Here, we investigated the role of family with sequence similarity 111 member B (FAM111B), which is highly expressed in papillary‐predominant LUAD; however, its role in cancer is unclear. An immunohistochemical analysis confirmed that papillary‐predominant adenocarcinomas exhibited higher expression of FAM111B, compared with lepidic‐predominant adenocarcinomas. Additionally, FAM111B expression was significantly correlated with clinical progression. In vitro functional analyses using FAM111B‐knockout cells demonstrated that FAM111B plays an important role in proliferation and cell cycle progression of KRAS ‐driven LUAD under serum‐starvation conditions. Furthermore, FAM111B regulated cyclin D1‐CDK4‐dependent cell cycle progression by degradation of p16. In summary, we revealed the clinical importance of FAM111B in human tumor tissues, as well as its function as a degradative enzyme. Therefore, FAM111B has potential as a clinicopathological prognostic marker for LUAD.