Department of Medical Laboratory, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Pathology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
ASN Neuro. 2021 Jan-Dec;13:17590914211001218. doi: 10.1177/17590914211001218.
ANXA1, which can bind phospholipid in a calcium dependent manner, is reported to play a pivotal role in tumor progression. However, the role and mechanism of ANXA1 involved in the occurrence and development of malignant glioma are still not well studied. Therefore, we explored the effects of ANXA1 on normal astrocytes and glioma cell proliferation, apoptosis, migration and invasion and the underlying mechanisms. We found that ANXA1 was markedly up-regulated in glioma cell lines and glioma tissues. Down-regulation of ANXA1 inhibited normal astrocytes and glioma cell proliferation and induced the cell apoptosis, which suggested that the consequences of loss of Annexin 1 are not specific to the tumor cells. Furthermore, the siRNA-ANXA1 treatment significantly reduced tumor growth rate and tumor weight. Moreover, decreasing ANXA1 expression caused G2/M phase arrest by repressing expression levels of cdc25C, cdc2 and cyclin B1. Interestingly, ANXA1 did not affect the expressions of β-catenin, GSK-3β and NF-κB, the key signaling molecules associated with cancer progression. However, siRNA-ANXA1 was found to negatively regulate phosphorylation of AKT and the expression and activity of MMP2/-9. Finally, the decrease of cell proliferation and invasiveness induced by ANXA1 down-regulation was partially reversed by combined treatment with AKT agonist insulin-like growth factor-1 (IGF-1). Meanwhile, the inhibition of glioma cell proliferation and invasiveness induced by ANXA1 down-regulation was further enhanced by combined treatment with AKT inhibitor LY294002. In summary, these findings demonstrate that ANXA1 regulates proliferation, migration and invasion of glioma cells via PI3K/AKT signaling pathway.
膜联蛋白 A1（ANXA1）能够以依赖钙离子的方式结合磷脂，据报道其在肿瘤进展中发挥关键作用。然而，ANXA1 在恶性脑胶质瘤发生发展中的作用和机制仍未得到充分研究。因此，我们探讨了 ANXA1 对正常星形胶质细胞和神经胶质瘤细胞增殖、凋亡、迁移和侵袭的影响及其潜在机制。我们发现，ANXA1 在神经胶质瘤细胞系和神经胶质瘤组织中明显上调。下调 ANXA1 抑制正常星形胶质细胞和神经胶质瘤细胞的增殖并诱导细胞凋亡，这表明 Annexin 1 的缺失后果并非肿瘤细胞所特有。此外，siRNA-ANXA1 处理显著降低了肿瘤生长速度和肿瘤重量。此外，降低 ANXA1 表达通过抑制 cdc25C、cdc2 和 cyclin B1 的表达水平导致 G2/M 期阻滞。有趣的是，ANXA1 不影响与癌症进展相关的关键信号分子β-catenin、GSK-3β 和 NF-κB 的表达。然而，发现 siRNA-ANXA1 负调控 AKT 的磷酸化以及 MMP2/-9 的表达和活性。最后，用 AKT 激动剂胰岛素样生长因子-1（IGF-1）联合处理部分逆转了 ANXA1 下调引起的细胞增殖和侵袭性降低。同时，用 AKT 抑制剂 LY294002 联合处理进一步增强了 ANXA1 下调诱导的神经胶质瘤细胞增殖和侵袭性抑制。总之，这些发现表明 ANXA1 通过 PI3K/AKT 信号通路调节神经胶质瘤细胞的增殖、迁移和侵袭。
