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Robert Liefke: Exploiting the tumor-suppressive role of the transcriptional repressor SAMD1 in pancreatic ductal adenocarcinoma (PDAC)

AIM: Our previous work identified SAM domain-containing protein 1 (SAMD1) as a tumor-suppressing chromatin regulator in pancreatic cancer. We will now explore its tumor-suppressive function in further detail with a focus on SAMD1-dependent secretome mediators and consequences for the TME composition. To this end, we plan to investigate the impact of SAMD1-mediated changes in gene expression on cellular properties, including the phenotype of non-malignant cells in the TME spheroid co-cultures in mouse models. Moving forward, our research aims to understand the precise role of SAMD1 in PDAC, with the ultimate goal of modulating its function.

STATE of the ART: EMT is a major driver of PDAC migration, invasion, and metastasis as well as drug resistance, leading to poor treatment outcomes and reduced survival rates. Recent studies have highlighted the significant role of repressive chromatin regulatory proteins, such as the polycomb repressive complex 2 (PRC2) enzyme EZH2, in modulating EMT [109]. Researchers are actively exploring various epigenetic mechanisms involved in the regulation of EMT, intending to discover new treatment strategies for PDAC [107]. We hypothesize that enhancing the tumor-suppressive function of SAMD1 can effectively inhibit the aggressiveness and metastatic potential of pancreatic cancer cells through the inhibition of EMT and secretome-mediated mechanisms.