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

尽管近年来取得了所有科学和临床进展，但非小细胞肺癌（NSCLC）的癌症特异性死亡率仍高达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。对于绝大多数在疾病晚期诊断的NSCLC患者，可用的治疗选择仅为姑息治疗。因此，迫切需要更好地了解导致NSCLC进展和转移的机制，以及确定适合于未来NSCLC治疗开发的新靶点。近年来，我们对这些问题进行了密切的研究，发现AAA + ATP酶Reptin在NSCLC中经常过表达，高表达与这些患者的预后不良高度显著相关。来自我们研究小组的其他数据表明，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疗法开发的靶点。然而，Reptin如何促进NSCLC的肿瘤发生和肿瘤进展的机制仍不清楚。由于Reptin经常与多蛋白复合物结合，我们项目的主要目的是详细说明NSCLC细胞中这种复合物的组成及其在这种疾病中的功能作用，以及检查这些组分的治疗效用。

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.