Clara Simon, Inka D Brunke, Bastian Stielow, Ignasi Forné, Anna Mary Steitz, Merle Geller, Iris Rohner, Lisa Marie Weber, Sabrina Fischer, Lea Marie Jeude, Theresa Huber, Andrea Nist, Thorsten Stiewe, Magdalena Huber, Malte Buchholz, Robert Liefke
PLoS biology 2024 AugPancreatic ductal adenocarcinoma (PDAC) poses a significant threat due to its tendency to evade early detection, frequent metastasis, and the subsequent challenges in devising effective treatments. Processes that govern epithelial-mesenchymal transition (EMT) in PDAC hold promise for advancing novel therapeutic strategies. SAMD1 (SAM domain-containing protein 1) is a CpG island-binding protein that plays a pivotal role in the repression of its target genes. Here, we revealed that SAMD1 acts as a repressor of genes associated with EMT. Upon deletion of SAMD1 in PDAC cells, we observed significantly increased migration rates. SAMD1 exerts its effects by binding to specific genomic targets, including CDH2, encoding N-cadherin, which emerged as a driver of enhanced migration upon SAMD1 knockout. Furthermore, we discovered the FBXO11-containing E3 ubiquitin ligase complex as an interactor and negative regulator of SAMD1, which inhibits SAMD1 chromatin-binding genome-wide. High FBXO11 expression in PDAC is associated with poor prognosis and increased expression of EMT-related genes, underlining an antagonistic relationship between SAMD1 and FBXO11. In summary, our findings provide insights into the regulation of EMT-related genes in PDAC, shedding light on the intricate role of SAMD1 and its interplay with FBXO11 in this cancer type. Copyright: © 2024 Simon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Clara Simon, Inka D Brunke, Bastian Stielow, Ignasi Forné, Anna Mary Steitz, Merle Geller, Iris Rohner, Lisa Marie Weber, Sabrina Fischer, Lea Marie Jeude, Theresa Huber, Andrea Nist, Thorsten Stiewe, Magdalena Huber, Malte Buchholz, Robert Liefke. SAMD1 suppresses epithelial-mesenchymal transition pathways in pancreatic ductal adenocarcinoma. PLoS biology. 2024 Aug;22(8):e3002739
PMID: 39137238
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