The Role of Amyloidogenesis in Cancer Development: An Investigation of Transcription Factors ^†

Cancer remains the leading cause of death due to a wide range of molecular mechanisms. One of these mechanisms is impaired proteostasis, which leads to the formation of amyloids, fibrillar proteins with an intermolecular cross-beta structure. Studies have shown that amyloids and amyloidogenic proteins are associated with tumor progression. For example, elevated levels of SAA amyloid in serum correlates with the development of lung, breast cancer, and melanoma. Similarly, the IAPP protein is associated with neuroendocrine tumors, and ODAM is associated with odontogenic tumors [1]. By using bioinformatics algorithms, we identified the amyloidogenic potential of five transcription factors involved in the pathogenesis of various cancers. Experimental testing of the amyloidogenic potential of these proteins in a yeast assay [2] partially confirmed the in silico data. The goal of this study was to further investigate the amyloid potential of these proteins in vitro. We employed the bacterial C-DAG production and export system [3] and/or purified recombinant proteins from E. coli with metal-affinity chromatography. For transcription factors that demonstrated amyloidogenic potential in bacteria, we analyzed their amyloid-like properties in human HEK293T cell culture. The results obtained in this study provide new insights into human proteins capable of forming amyloids and offer promising prospects for identifying potential targets for cancer therapy.