B7 family member H4 induces epithelial-mesenchymal transition and promotes the proliferation, migration and invasion of colorectal cancer cells

Colorectal cancer (CRC) is a common malignancy of the gastrointestinal tract, which has the second highest incidence among gastrointestinal tumors. At present, due to the limitations of current CRC treatment strategies, there is an urgent need for developing more effective therapies. B7 family member H4 (B7-H4) is associated with the progression of a wide spectrum of cancers, but its functional role in CRC is unknown. The purpose of this study is to clarify the role of B7-H4 in CRC and the underlying mechanisms in controlling the progression of CRC. Our data showed that B7-H4 expression in CRC tissues and cell lines was significantly upregulated as compared with normal tissues and normal cell lines. High B7-H4 expression was correlated with a poor prognosis of CRC patients. B7-H4 overexpression promoted the proliferation and invasion of CRC cells, which could be suppressed by Wnt signaling inhibitor. In a mouse xenograft model, silencing B7-H4 suppressed tumor growth and epithelial–mesenchymal transition (EMT) of CRC cells. Collectively, our study demonstrated the oncogenic roles of B7-H4 in regulating the proliferation, EMT as well as the migration of CRC cells through Wnt signaling pathway. The heightened expression of B7-H4 could serve as a prognostic marker for CRC patients.

结直肠癌（Colorectal cancer, CRC）是一类常见的胃肠道恶性肿瘤，其发病率在胃肠道肿瘤中位居第二。当前，受限于现有的结直肠癌治疗策略，临床上迫切需要开发更为有效的治疗手段。B7家族成员H4（B7 family member H4, B7-H4）与多种癌症的进展密切相关，但其在结直肠癌中的功能作用尚未明确。本研究旨在阐明B7-H4在结直肠癌中的作用及其调控结直肠癌进展的潜在机制。研究数据显示，相较于正常组织及正常细胞系，结直肠癌组织与细胞系中B7-H4的表达显著上调。高表达B7-H4与结直肠癌患者的不良预后显著相关。B7-H4过表达可促进结直肠癌细胞的增殖与侵袭，该效应可被Wnt信号通路抑制剂所抑制。在小鼠异种移植模型中，敲低B7-H4可抑制结直肠癌细胞的肿瘤生长及上皮间质转化（epithelial–mesenchymal transition, EMT）。综上，本研究证实B7-H4可通过Wnt信号通路调控结直肠癌细胞的增殖、上皮间质转化及迁移，发挥致癌作用。B7-H4的高表达可作为结直肠癌患者的预后标志物。