Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Acta Biochim Biophys Sin (Shanghai). 2022 Mar 25;54(3):361-369. doi: 10.3724/abbs.2022015.
Pancreatic cancer is highly lethal due to its aggressive invasive properties and capacity for metastatic dissemination. Additional therapeutic targets and effective treatment options for patients with tumours of high invasive capacity are required. Ras-related protein-2a (RAP2) is a member of the GTP-binding proteins. RAP2 has been reported to be widely upregulated in many types of cancers via regulating cytoskeleton reorganization, cell proliferation, migration, and adhesion, as well as inflammation. As a member of the RAS oncogene family, which has been demonstrated to drive pancreatic cancer oncogenesis and many other malignancies, the physiological roles of RAP2 in pancreatic cancer have seldom been discussed. In the present study, we explored the correlation between RAP2 expression and the prediction of overall survival of pancreatic cancer patients. Mechanistic studies were carried out to shed light on the role of RAP2 in pancreatic cancer invasion and how RAP2 is regulated in the invasive process. Our results demonstrated that patients with higher RAP2 expression showed unfavourable prognoses. studies demonstrated that silencing of inhibited the invasion of pancreatic cancer cells. Moreover, our results demonstrated that transforming growth factor-β1 (TGF-β1), an inducer of the metastatic potential of pancreatic cancer cells, regulates the expression of RAP2 via the transcription factor c-Myc. In conclusion, the present study uncovered RAP2 as a novel predictive marker and therapeutic target for pancreatic cancer.
由于其侵袭性和转移性扩散的能力，胰腺癌的致死率很高。因此，需要寻找更多的治疗靶点和有效的治疗方案，以满足具有高侵袭性肿瘤的患者的需求。Ras 相关蛋白-2a（RAP2）是 GTP 结合蛋白家族的成员。有研究报道，RAP2 通过调节细胞骨架重组、细胞增殖、迁移和黏附以及炎症等过程，在多种癌症中广泛上调。作为 Ras 癌基因家族的成员之一，它已被证明可以驱动胰腺癌的发生和许多其他恶性肿瘤的发生，但其在胰腺癌中的生理作用很少被讨论。在本研究中，我们探讨了 RAP2 表达与胰腺癌患者总生存期预测的相关性。通过进行机制研究，阐明了 RAP2 在胰腺癌侵袭中的作用，以及 RAP2 在侵袭过程中的调控机制。我们的结果表明，RAP2 高表达的患者预后较差。研究表明，沉默抑制了胰腺癌细胞的侵袭。此外，我们的结果表明，转化生长因子-β1（TGF-β1）是一种诱导胰腺癌细胞转移潜能的物质，通过转录因子 c-Myc 调节 RAP2 的表达。总之，本研究揭示了 RAP2 是一种新的预测标志物和治疗靶点，可用于胰腺癌的治疗。
