Department of Respiratory Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No.301, Mid Yanchang Rd, Shanghai, 200072, People's Republic of China.
J Cancer Res Clin Oncol. 2022 Jan;148(1):137-153. doi: 10.1007/s00432-021-03819-9. Epub 2021 Oct 12.
Cyclase-associated protein 1 (CAP1) is a ubiquitous protein which regulates actin dynamics. Previous studies have shown that S308 and S310 are the two major phosphorylated sites in human CAP1. In the present study, we aimed to investigate the role of CAP1 phosphorylation in lung cancer.
Massive bioinformatics analysis was applied to determine CAP1's role in different cancers and especially in lung cancer. Lung cancer patients' serum and tissue were collected and analyzed in consideration of clinical background. CAP1 shRNA-lentivirus and siRNA were applied to CAP1 gene knockdown, and plasmids were constructed for CAP1 phosphorylation and de-phosphorylation. Microarray analysis was used for CAP1-associated difference analysis. Both in vitro and in vivo experiments were performed to investigate the roles of CAP1 phosphorylation and de-phosphorylation in lung cancer A549 cells.
CAP1 is a kind of cancer-related protein. Its mRNA was overexpressed in most types of cancer tissues when compared with normal tissues. CAP1 high expression correlated with poor prognosis. Our results showed that serum CAP1 protein concentrations were significantly upregulated in non-small cell lung cancer (NSCLC) patients when compared with the healthy control group, higher serum CAP1 protein concentration correlated with shorter overall survival (OS) in NSCLC patients, and higher pCAP1 and CAP1 protein level were observed in lung cancer patients' tumor tissue compared with adjacent normal tissue. Knockdown CAP1 in A549 cells can inhibit proliferation and migration, and the effect is validated in H1975 cells. It can also lead to an increase ratio of F-actin/G-actin. In addition, phosphorylated S308 and S310 in CAP1 promoted lung cancer cell proliferation, migration, and metastasis both in vitro and in vivo. When de-phosphorylated, these two sites in CAP1 showed the opposite effect. Phosphorylation of CAP1 can promote epithelial-mesenchymal transition (EMT).
These findings indicated that CAP1 phosphorylation can promote lung cancer proliferation, migration, and invasion. Phosphorylation sites of CAP1 might be a novel target for lung cancer treatment.
环化酶相关蛋白 1（CAP1）是一种普遍存在的蛋白质，可调节肌动蛋白动力学。先前的研究表明，人 CAP1 的 S308 和 S310 是两个主要的磷酸化位点。本研究旨在探讨 CAP1 磷酸化在肺癌中的作用。
采用大量生物信息学分析方法确定 CAP1 在不同癌症中的作用，特别是在肺癌中的作用。收集并分析肺癌患者的血清和组织，并考虑临床背景。应用 CAP1 shRNA-慢病毒和 siRNA 敲低 CAP1 基因，构建 CAP1 磷酸化和去磷酸化质粒。应用微阵列分析进行 CAP1 相关差异分析。进行体外和体内实验，研究 CAP1 磷酸化和去磷酸化在肺癌 A549 细胞中的作用。
CAP1 是一种与癌症相关的蛋白质。与正常组织相比，其 mRNA 在大多数类型的癌症组织中过度表达。CAP1 高表达与预后不良相关。我们的结果表明，与健康对照组相比，非小细胞肺癌（NSCLC）患者的血清 CAP1 蛋白浓度显著升高，NSCLC 患者血清 CAP1 蛋白浓度越高，总生存期（OS）越短，与相邻正常组织相比，肺癌患者肿瘤组织中 pCAP1 和 CAP1 蛋白水平更高。在 A549 细胞中敲低 CAP1 可以抑制增殖和迁移，在 H1975 细胞中得到验证。它还可以导致 F-肌动蛋白/G-肌动蛋白的比值增加。此外，CAP1 的磷酸化 S308 和 S310 可促进肺癌细胞在体外和体内的增殖、迁移和转移。去磷酸化后，CAP1 的这两个位点则表现出相反的作用。CAP1 的磷酸化可促进上皮-间充质转化（EMT）。
这些发现表明，CAP1 磷酸化可促进肺癌的增殖、迁移和侵袭。CAP1 的磷酸化位点可能是肺癌治疗的新靶点。
