GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China.
Key Laboratory of Protein Modification and Degradation School of Basic Medical Sciences, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China.
Mol Cancer Res. 2018 Oct;16(10):1512-1522. doi: 10.1158/1541-7786.MCR-18-0157. Epub 2018 Jul 2.
Calcineurin B homologous protein isoform 2 (CHP2), an essential cofactor for Na/H exchanger isoform 1 (NHE1), is identified to be expressed in various malignant cell lines. However, the clinical significance and biological role of CHP2 in breast cancer remain to be established. Here, CHP2 was markedly overexpressed in breast cancer cells and clinical tumor specimens. Immunohistochemical analysis revealed that the expression of CHP2 was significantly correlated with patients' clinicopathologic characteristics like clinical stage, and breast cancer patients with high CHP2 expression had shorter overall survival compared with patients with low CHP2 expression. Moreover, it was demonstrated that overexpressing CHP2 significantly enhanced, whereas silencing endogenous CHP2 inhibited, the proliferation and tumorigenicity of breast cancer cells and In addition, overexpression of CHP2 accelerated, whereas inhibition of CHP2 retarded, G-S phase cell-cycle transition in breast cancer cells. Mechanistically, overexpression of CHP2 activated AKT signaling and suppressed the transactivation of the forkhead box O3 (FOXO3/FOXO3a) transcription factor. This study discovers a previously unrecognized role of CHP2 in the progression of breast cancer and supports the significance of this gene as a novel prognostic biomarker and a potential therapeutic target for breast cancer. .
钙调磷酸酶 B 同源蛋白同种型 2（CHP2）是 Na/H 交换体同种型 1（NHE1）的必需辅助因子，已被鉴定在各种恶性细胞系中表达。然而，CHP2 在乳腺癌中的临床意义和生物学作用仍有待确定。在这里，CHP2 在乳腺癌细胞和临床肿瘤标本中明显过表达。免疫组织化学分析显示，CHP2 的表达与患者的临床病理特征显著相关，如临床分期，高 CHP2 表达的乳腺癌患者的总生存期明显短于低 CHP2 表达的患者。此外，研究表明，过表达 CHP2 显著增强，而沉默内源性 CHP2 抑制乳腺癌细胞的增殖和致瘤性，并且过表达 CHP2 加速，而抑制 CHP2 延迟，乳腺癌细胞的 G1-S 期细胞周期转换。在机制上，CHP2 的过表达激活了 AKT 信号通路，并抑制了叉头框 O3（FOXO3/FOXO3a）转录因子的反式激活。本研究发现了 CHP2 在乳腺癌进展中的一个以前未被认识的作用，并支持该基因作为一种新的预后生物标志物和乳腺癌潜在治疗靶点的重要性。
