> Detailanzeige

Liebig, Sven; Neumann, Martin; Silva, Patricia; Ortiz-Tanchez, Jutta; Schulze, Veronika; Isaakidis, Konstandina; Schlee, Cornelia; Schroeder, Michael P.; Beder, Thomas; Morris, Luc G. T.; Chan, Timothy A.; Bastian, Lorenz; Burmeister, Thomas; Schwartz, Stefan; Gökbuget, Nicola; Mochmann, Liliana H.; Baldus, Claudia D.

FAT1 expression in T-cell acute lymphoblastic leukemia (T-ALL) modulates proliferation and WNT signaling

Literatur-
verwaltung

Zur
Merkliste

Lösche von
Merkliste

Per Whatsapp teilen

Schließen

Merkliste



Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
  • Medientyp: E-Artikel
  • Titel: FAT1 expression in T-cell acute lymphoblastic leukemia (T-ALL) modulates proliferation and WNT signaling
  • Beteiligte: Liebig, Sven; Neumann, Martin; Silva, Patricia; Ortiz-Tanchez, Jutta; Schulze, Veronika; Isaakidis, Konstandina; Schlee, Cornelia; Schroeder, Michael P.; Beder, Thomas; Morris, Luc G. T.; Chan, Timothy A.; Bastian, Lorenz; Burmeister, Thomas; Schwartz, Stefan; Gökbuget, Nicola; Mochmann, Liliana H.; Baldus, Claudia D.
  • Erschienen: Springer Science and Business Media LLC, 2023
  • Erschienen in: Scientific Reports
  • Sprache: Englisch
  • DOI: 10.1038/s41598-023-27792-0
  • ISSN: 2045-2322
  • Schlagwörter: Multidisciplinary
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>FAT atypical cadherin 1 (FAT1), a transmembrane protein, is frequently mutated in various cancer types and has been described as context-dependent tumor suppressor or oncogene. The <jats:italic>FAT1</jats:italic> gene is mutated in 12–16% of T-cell acute leukemia (T-ALL) and aberrantly expressed in about 54% of T-ALL cases contrasted with absent expression in normal T-cells. Here, we characterized <jats:italic>FAT1</jats:italic> expression and profiled the methylation status from T-ALL patients. In our T-ALL cohort, 53% of patient samples were <jats:italic>FAT1</jats:italic> positive (FAT1pos) compared to only 16% <jats:italic>FAT1</jats:italic> positivity in early T-ALL patient samples. Aberrant expression of <jats:italic>FAT1</jats:italic> was strongly associated with <jats:italic>FAT1</jats:italic> promotor hypomethylation, yet a subset, mainly consisting of TLX1-driven T-ALL patient samples showed methylation-independent high <jats:italic>FAT1</jats:italic> expression. Genes correlating with <jats:italic>FAT1</jats:italic> expression revealed enrichment in WNT signaling genes representing the most enriched single pathway. <jats:italic>FAT1</jats:italic> knockdown or knockout led to impaired proliferation and downregulation of WNT pathway target genes (<jats:italic>CCND1</jats:italic>, <jats:italic>MYC</jats:italic>, <jats:italic>LEF1)</jats:italic>, while <jats:italic>FAT1</jats:italic> overexpressing conveyed a proliferative advantage. To conclude, we characterized a subtype pattern of <jats:italic>FAT1</jats:italic> gene expression in adult T-ALL patients correlating with promotor methylation status. <jats:italic>FAT1</jats:italic> dependent proliferation and WNT signaling discloses an impact on deeper understanding of T-ALL leukemogenesis as a fundament for prospective therapeutic strategies.</jats:p>
  • Zugangsstatus: Freier Zugang