Uncovering the role of the Reptin/Pontin multiprotein complex in Non-Small Cell Lung Cancer (NSCLC)

尽管近年来在科学和临床方面取得了很大进展，但非小细胞肺癌(NSCLC)的癌症特异性死亡率仍然高达80%。非小细胞肺癌是德国所有恶性疾病中死亡率最高的一种。对于绝大多数被诊断为疾病晚期的非小细胞肺癌患者，可用的治疗方案只能是姑息性的。因此，迫切需要更好地了解导致非小细胞肺癌进展和转移的机制，以及寻找适合于未来非小细胞肺癌治疗的新靶点。近年来，我们在这些问题上进行了密切的合作，并发现AAA+ATPase Reptin在NSCLC中经常过表达，高表达与这些患者的预后不良密切相关。来自我们研究组的更多数据表明，Reptin的表达对NSCLC细胞的增殖和生长至关重要，Reptin驱动的信号通路也可能成为未来NSCLC治疗的靶点。然而，Reptin在非小细胞肺癌发生和发展中的作用机制尚不清楚。由于Reptin经常与多蛋白质复合体结合，我们项目的关键目标是详细说明NSCLC细胞中这种复合体的组成及其在这种疾病中的功能作用，以及检查这些成分的治疗作用。

Despite all scientific and clinical advances in recent years, the cancer-specific mortality of non-small cell lung cancer (NSCLC) remains high at 80%. NSCLC is the one with the highest mortality among all malignant diseases in Germany. For the vast majority of NSCLC patients diagnosed at advanced stage of the disease the available treatment options are only palliative. Therefore, there is an urgent need for better understanding of the mechanisms leading to progression and metastasis of NSCLC as well as to identify novel targets suitable for the development of future NSCLC therapies. In recent years, we have worked closely on these questions and have shown that the AAA + ATPase Reptin is frequently overexpressed in NSCLC and high expression is highly significantly associated with a poorer prognosis of these patients. Additional data from our research group indicate that expression of Reptin is critical for proliferation and growth of NSCLC cells, and that Reptin-driven signaling pathways may also serve as targets for the development of future NSCLC therapies. However, the mechanisms how Reptin contributes to oncogenesis and tumor progression of NSCLC is still unknown. Since Reptin frequently associates in multi-protein complexes, the key aim of our project is to detail the composition of this complex in NSCLC cells and its functional role in this disease, as well as to examine the therapeutic utility of these components.