Department of Radiology, Shibei hospital of Jing'an District of Shanghai, Shanghai, China.
Department of Radiology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Mol Carcinog. 2020 May;59(5):533-544. doi: 10.1002/mc.23177. Epub 2020 Mar 17.
Elevated expression of Copine 1 (CPNE1) has been observed in multiple cancers; however, the underlying mechanisms by which it affects cancer cells are unclear. We aimed to study the effect of CPNE1 on the tumorigenesis and radioresistance of triple-negative breast cancer (TNBC). Quantitative real-time polymerase chain reaction was used to detect the expression of CPNE1 in TNBC tissues and cell lines. Western blot, immunohistochemistry, and immunofluorescence were used to investigate the levels of CPNE1, p-AKT, AKT, cleaved caspase-3, cleaved PARP1, and γ-H2AX. Cell viability and apoptosis were measured by CCK-8 and flow cytometry, respectively. CPNE1 was overexpressed in TNBC tissues and cell lines and was associated with tumor size, distant metastases, and survival rates of patients with TNBC. Moreover, function study shows that CPNE1 promoted cell viability and inhibited cell apoptosis in vitro and inhibited the radiosensitivity of TNBC. Importantly, inactivation of AKT signaling inhibited the tumorigenesis and radioresistance mediated by CPNE1 in TNBC cells. In vivo xenograft study also shows that CPNE1 knockdown inhibited tumor growth and promoted cell apoptosis. Overall, our findings suggest that CPNE1 promotes tumorigenesis and radioresistance in TNBC by regulating AKT activation and targeted CPNE1 expression may be a strategy to sensitize TNBC cells toward radiation therapy.
Copine 1（CPNE1）的表达升高已在多种癌症中观察到；然而，其影响癌细胞的潜在机制尚不清楚。我们旨在研究 CPNE1 对三阴性乳腺癌（TNBC）的肿瘤发生和放射抵抗的影响。实时定量聚合酶链反应用于检测 TNBC 组织和细胞系中 CPNE1 的表达。Western blot、免疫组织化学和免疫荧光用于研究 CPNE1、p-AKT、AKT、cleaved caspase-3、cleaved PARP1 和 γ-H2AX 的水平。通过 CCK-8 和流式细胞术分别测量细胞活力和细胞凋亡。CPNE1 在 TNBC 组织和细胞系中过表达，与 TNBC 患者的肿瘤大小、远处转移和生存率相关。此外，功能研究表明 CPNE1 在体外促进细胞活力并抑制细胞凋亡，抑制 TNBC 的放射敏感性。重要的是，AKT 信号通路的失活抑制了 CPNE1 在 TNBC 细胞中介导的肿瘤发生和放射抵抗。体内异种移植研究也表明 CPNE1 敲低抑制肿瘤生长并促进细胞凋亡。总体而言，我们的研究结果表明，CPNE1 通过调节 AKT 激活促进 TNBC 的肿瘤发生和放射抵抗，靶向 CPNE1 表达可能是一种使 TNBC 细胞对放射治疗敏感的策略。
