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

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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.