Chromobox 4 facilitates tumorigenesis of lung adenocarcinoma through the Wnt/β-catenin pathway

Zuoyun Wang; Zhaoyuan Fang; Gaobin Chen; Bo Liu; Jinjin Xu; Fei Li; Fuming Li; Hongyan Liu; Haoen Zhang; Yihua Sun; Gang Tian; Haiquan Chen; Guoliang Xu; Lei Zhang; Liang Hu; Hongbin Ji

Neoplasia: An International Journal for Oncology Research (Feb 2021)

Chromobox 4 facilitates tumorigenesis of lung adenocarcinoma through the Wnt/β-catenin pathway

Zuoyun Wang,
Zhaoyuan Fang,
Gaobin Chen,
Bo Liu,
Jinjin Xu,
Fei Li,
Fuming Li,
Hongyan Liu,
Haoen Zhang,
Yihua Sun,
Gang Tian,
Haiquan Chen,
Guoliang Xu,
Lei Zhang,
Liang Hu,
Hongbin Ji

Affiliations

Zuoyun Wang: State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China; Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China; Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China
Zhaoyuan Fang: State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China; Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China; Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China
Gaobin Chen: State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China; Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China; Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China
Bo Liu: CAS Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China
Jinjin Xu: State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China; Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China; Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China
Fei Li: State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China; Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China; Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China
Fuming Li: State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China; Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China; Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China
Hongyan Liu: State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China; Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China; Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China
Haoen Zhang: State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China; Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China; Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China
Yihua Sun: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
Gang Tian: School of Life Science and Technology, Shanghai Tech University, Shanghai, China
Haiquan Chen: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China
Guoliang Xu: Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China; Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China
Lei Zhang: State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China; Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China; Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China; School of Life Science and Technology, Shanghai Tech University, Shanghai, China
Liang Hu: State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China; Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China; Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China; Corresponding authors.
Hongbin Ji: State Key Laboratory of Cell Biology, Chinese Academy of Sciences, Shanghai, China; Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China; Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China; School of Life Science and Technology, Shanghai Tech University, Shanghai, China; Corresponding authors.

Journal volume & issue: Vol. 23, no. 2
pp. 222 – 233

Abstract

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Chromobox 4 (CBX4) is a core component of polycomb-repressive complex 1 with important roles in cancer biology and tissue homeostasis. Aberrant expression of CBX4 has been implicated in several human malignancies. However, its role and underlying mechanisms in the tumorigenesis of lung adenocarcinoma (LUAD) have not been defined in vivo. Here, we found that expression of CBX4 was frequently up-regulated in human LUAD samples and correlated with poor patient survival. Importantly, genetic ablation of CBX4 greatly dampened lung tumor formation and improved survival in the KrasG12D/P53L/L (KP) autochthonous mouse model of LUAD. In addition, CBX4 depletion significantly inhibited proliferation and anchorage-independent growth of KP mouse embryonic fibroblasts. Moreover, ectopic CBX4 expression clearly promoted proliferation and anchorage-independent growth in both human and mouse LUAD cells, whereas silencing of CBX4 exerted opposite effects. Mechanistically, CBX4 promoted growth of LUAD cells through activation of the Wnt/β-catenin pathway. Furthermore, expression levels of CBX4 were positively correlated with β-catenin in human LUAD samples. In conclusion, our data suggest that CBX4 plays an oncogenic role via the Wnt/β-catenin pathway and could serve as a potential therapeutic target in LUAD.

Published in Neoplasia: An International Journal for Oncology Research

ISSN: 1522-8002 (Print); 1476-5586 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.journals.elsevier.com/neoplasia/

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