Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
J Bioenerg Biomembr. 2021 Jun;53(3):295-305. doi: 10.1007/s10863-021-09891-7. Epub 2021 Mar 12.
Lung cancer, the most concerning malignancy worldwide and one of the leading causes of cancer-related deaths. Growing evidence indicates that Angiomotin (Amot)-p130 plays an important role in types of cancer, including breast cancer and gastric cancer. Moreover, evidence suggested that the low Amot-p130 expression correlates with the poor prognosis of lung cancer patients, however, the role and mechanism of Amot-p130 in lung cancer is still unclear. In this study, we showed that Amot-p130 expression was reduced in lung cancer tissues, compared with the adjacent para-carcinoma tissues. In addition, we observed that the reduced expression of Amot-p130 was associated with vasculogenic mimicry (VM) channels formation in lung cancer tissues. Amot-p130 expression was differently expression in lung cancer cell line H446, H1688 and H2227 compared with the normal human lung cells HFL1. To clarify the role of Amot-p130 in lung cancer, we constructed the Amot-p130 expressing H446 cells and Amot-p130 silencing H1299 cells. We confirmed that Amot-p130 overexpression inhibited the migration and invasion of lung cancer cells, whereas its silence promoted cell migration and invasion. Interestingly, we also found that Amot-p130 overexpression suppressed VM tube formation in H446 cells, while its knockdown promoted VM tube formation in H2227 cells. Further studies suggested that Amot-p130 plays roles in M tube formation of lung cancer cell V are independent on smad2/3 signaling pathway. Finally, inoculation of Amot-p130 expressing H446 cells and Amot-p130 silencing H1299 cells into nude mice suppressed tumor growth, when compared with the control group. Based on these results, Amot-p130 serves as a possible diagnostic and therapeutic target in lung cancer patients, and may be an effective mediator of VM formation in lung cancer.
肺癌是全球最令人担忧的恶性肿瘤之一，也是癌症相关死亡的主要原因之一。越来越多的证据表明，血管生成素（Angiomotin）-p130 在包括乳腺癌和胃癌在内的多种癌症中发挥着重要作用。此外，有证据表明，Amot-p130 表达水平低与肺癌患者的预后不良相关，但 Amot-p130 在肺癌中的作用和机制尚不清楚。在本研究中，我们发现与癌旁组织相比，肺癌组织中 Amot-p130 的表达降低。此外，我们观察到 Amot-p130 的表达减少与肺癌组织中血管生成拟态（VM）通道的形成有关。与正常肺细胞 HFL1 相比，Amot-p130 在肺癌细胞系 H446、H1688 和 H2227 中的表达不同。为了阐明 Amot-p130 在肺癌中的作用，我们构建了 Amot-p130 表达的 H446 细胞和 Amot-p130 沉默的 H1299 细胞。我们证实 Amot-p130 过表达抑制了肺癌细胞的迁移和侵袭，而其沉默则促进了细胞的迁移和侵袭。有趣的是，我们还发现 Amot-p130 过表达抑制了 H446 细胞中 VM 管的形成，而其敲低则促进了 H2227 细胞中 VM 管的形成。进一步的研究表明，Amot-p130 在肺癌细胞 VM 管形成中的作用不依赖于 smad2/3 信号通路。最后，与对照组相比，接种 Amot-p130 表达的 H446 细胞和 Amot-p130 沉默的 H1299 细胞可抑制肿瘤生长。基于这些结果，Amot-p130 可作为肺癌患者的潜在诊断和治疗靶点，并可能成为肺癌中 VM 形成的有效介质。
