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SAMD1 suppresses epithelial-mesenchymal transition pathways in pancreatic ductal adenocarcinoma.
Simon, Clara; Brunke, Inka D; Stielow, Bastian; Forné, Ignasi; Steitz, Anna Mary; Geller, Merle; Rohner, Iris; Weber, Lisa Marie; Fischer, Sabrina; Jeude, Lea Marie; Huber, Theresa; Nist, Andrea; Stiewe, Thorsten; Huber, Magdalena; Buchholz, Malte; Liefke, Robert.
Afiliação
  • Simon C; Institute of Molecular Biology and Tumor Research (IMT), Philipps University of Marburg, Marburg, Germany.
  • Brunke ID; Institute of Molecular Biology and Tumor Research (IMT), Philipps University of Marburg, Marburg, Germany.
  • Stielow B; Institute of Molecular Biology and Tumor Research (IMT), Philipps University of Marburg, Marburg, Germany.
  • Forné I; Protein Analysis Unit, Biomedical Center (BMC), Faculty of Medicine, Ludwig-Maximilians-University (LMU) Munich, Martinsried, Germany.
  • Steitz AM; Translational Oncology Group, Center for Tumor Biology and Immunology (ZTI), Philipps University of Marburg, Marburg, Germany.
  • Geller M; Institute of Molecular Biology and Tumor Research (IMT), Philipps University of Marburg, Marburg, Germany.
  • Rohner I; Institute of Molecular Biology and Tumor Research (IMT), Philipps University of Marburg, Marburg, Germany.
  • Weber LM; Institute of Molecular Biology and Tumor Research (IMT), Philipps University of Marburg, Marburg, Germany.
  • Fischer S; Institute of Molecular Biology and Tumor Research (IMT), Philipps University of Marburg, Marburg, Germany.
  • Jeude LM; Institute of Molecular Biology and Tumor Research (IMT), Philipps University of Marburg, Marburg, Germany.
  • Huber T; Institute of Molecular Biology and Tumor Research (IMT), Philipps University of Marburg, Marburg, Germany.
  • Nist A; Genomics Core Facility, Institute of Molecular Oncology, Member of the German Center for Lung Research (DZL), Philipps University of Marburg, Marburg, Germany.
  • Stiewe T; Institute for Lung Health (ILH), Justus Liebig University, Giessen, Germany.
  • Huber M; Genomics Core Facility, Institute of Molecular Oncology, Member of the German Center for Lung Research (DZL), Philipps University of Marburg, Marburg, Germany.
  • Buchholz M; Institute for Lung Health (ILH), Justus Liebig University, Giessen, Germany.
  • Liefke R; Institute of Systems Immunology, Center for Tumor Biology and Immunology (ZTI), Philipps University of Marburg, Marburg, Germany.
PLoS Biol ; 22(8): e3002739, 2024 Aug.
Article em En | MEDLINE | ID: mdl-39137238
ABSTRACT
Pancreatic 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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Receptores de LDL / Regulação Neoplásica da Expressão Gênica / Carcinoma Ductal Pancreático / Proteínas F-Box / Transição Epitelial-Mesenquimal Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Receptores de LDL / Regulação Neoplásica da Expressão Gênica / Carcinoma Ductal Pancreático / Proteínas F-Box / Transição Epitelial-Mesenquimal Idioma: En Ano de publicação: 2024 Tipo de documento: Article