TY  - JOUR
A1  - Wallaschek, Nina
A1  - Reuter, Saskia
A1  - Silkenat, Sabrina
A1  - Wolf, Katharina
A1  - Niklas, Carolin
A1  - Özge, Kayisoglu
A1  - Aguilar, Carmen
A1  - Wiegering, Armin
A1  - Germer, Christoph-Thomas
A1  - Kircher, Stefan
A1  - Rosenwald, Andreas
A1  - Shannon-Lowe, Claire
A1  - Bartfeld, Sina
T1  - Ephrin receptor A2, the epithelial receptor for Epstein-Barr virus entry, is not available for efficient infection in human gastric organoids
JF  - PLoS Pathogens
N2  - Epstein-Barr virus (EBV) is best known for infection of B cells, in which it usually establishes an asymptomatic lifelong infection, but is also associated with the development of multiple B cell lymphomas. EBV also infects epithelial cells and is associated with all cases of undifferentiated nasopharyngeal carcinoma (NPC). EBV is etiologically linked with at least 8% of gastric cancer (EBVaGC) that comprises a genetically and epigenetically distinct subset of GC. Although we have a very good understanding of B cell entry and lymphomagenesis, the sequence of events leading to EBVaGC remains poorly understood. Recently, ephrin receptor A2 (EPHA2) was proposed as the epithelial cell receptor on human cancer cell lines. Although we confirm some of these results, we demonstrate that EBV does not infect healthy adult stem cell-derived gastric organoids. In matched pairs of normal and cancer-derived organoids from the same patient, EBV only reproducibly infected the cancer organoids. While there was no clear pattern of differential expression between normal and cancer organoids for EPHA2 at the RNA and protein level, the subcellular location of the protein differed markedly. Confocal microscopy showed EPHA2 localization at the cell-cell junctions in primary cells, but not in cancer cell lines. Furthermore, histologic analysis of patient tissue revealed the absence of EBV in healthy epithelium and presence of EBV in epithelial cells from inflamed tissue. These data suggest that the EPHA2 receptor is not accessible to EBV on healthy gastric epithelial cells with intact cell-cell contacts, but either this or another, yet to be identified receptor may become accessible following cellular changes induced by inflammation or transformation, rendering changes in the cellular architecture an essential prerequisite to EBV infection.
KW  - Organoids
KW  - ephitelial cells
KW  - gastrointestinal infections
KW  - cancers and neoplasms
KW  - Epstein-Barr virus
KW  - flow cytometry
KW  - epithelium
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259206
VL  - 17
IS  - 2
ER  - 
TY  - JOUR
A1  - Pattschull, Grit
A1  - Walz, Susanne
A1  - Gründl, Marco
A1  - Schwab, Melissa
A1  - Rühl, Eva
A1  - Baluapuri, Apoorva
A1  - Cindric-Vranesic, Anita
A1  - Kneitz, Susanne
A1  - Wolf, Elmar
A1  - Ade, Carsten P.
A1  - Rosenwald, Andreas
A1  - von Eyss, Björn
A1  - Gaubatz, Stefan
T1  - The Myb-MuvB complex is required for YAP-dependent transcription of mitotic genes
JF  - Cell Reports
N2  - YAP and TAZ, downstream effectors of the Hippo pathway, are important regulators of proliferation. Here, we show that the ability of YAP to activate mitotic gene expression is dependent on the Myb-MuvB (MMB) complex, a master regulator of genes expressed in the G2/M phase of the cell cycle. By carrying out genome-wide expression and binding analyses, we found that YAP promotes binding of the MMB subunit B-MYB to the promoters of mitotic target genes. YAP binds to B-MYB and stimulates B-MYB chromatin association through distal enhancer elements that interact with MMB-regulated promoters through chromatin looping. The cooperation between YAP and B-MYB is critical for YAP-mediated entry into mitosis. Furthermore, the expression of genes coactivated by YAP and B-MYB is associated with poor survival of cancer patients. Our findings provide a molecular mechanism by which YAP and MMB regulate mitotic gene expression and suggest a link between two cancer-relevant signaling pathways.
KW  - YAP
KW  - B-MYB
KW  - Myb-MuvB
KW  - mitotic genes
KW  - enhancer
KW  - transcription
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202039
VL  - 27
IS  - 12
ER  -