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

• DOI: 10.1016/j.neo.2020.12.005
• Publication Date: 2020-12-30T23:55:29Z
• Authors: 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
• Keywords: Lung adenocarcinoma; Gene Expression; Polycomb-Group Proteins; Adenocarcinoma of Lung; Ligases; Mice; 03 medical and health sciences; Cell Line, Tumor; Wnt/β-catenin pathway; Animals; Humans; Wnt Signaling Pathway; RC254-282; Original Research; Mice, Knockout; 0303 health sciences; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Prognosis; Immunohistochemistry; 3. Good health; Gene Expression Regulation, Neoplastic; Disease Models, Animal; Cell Transformation, Neoplastic; CBX4; Tumorigenesis; Disease Susceptibility

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.