Dual role of GRHL3 in bladder carcinogenesis depending on histological subtypes

© 2024 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies..

The effect of grainyhead-like transcription factor 3 (GRHL3) on cancer development depends on the cancer subtypes as shown in tumor entities such as colorectal or oral squamous cell carcinomas. Here, we analyzed the subtype-specific role of GRHL3 in bladder carcinogenesis, comparing common urothelial carcinoma (UC) with squamous bladder cancer (sq-BLCA). We examined GRHL3 mRNA and protein expression in cohorts of patient samples, its prognostic role and its functional impact on tumorigeneses in different molecular and histopathological subtypes of bladder cancer. We showed for GRHL3 a reverse expression in squamous and urothelial bladder cancer subtypes. Stably GRHL3-overexpressing EJ28, J82, and SCaBER in vitro models revealed a tumor-suppressive function in squamous and an oncogenic role in the urothelial cancer cells affecting cell and colony growth, and migratory and invasive capacities. Transcriptomic profiling demonstrated highly subtype-specific GRHL3-regulated expression networks coined by the enrichment of genes involved in integrin-mediated pathways. In SCaBER, loss of ras homolog family member A (RHOA) GTPase activity was demonstrated to be associated with co-regulation of eukaryotic translation initiation factor 4E family member 3 (EIF4E3), a potential tumor suppressor gene. Thus, our data provide for the first time a detailed insight into the role of the transcription factor GRHL3 in different histopathological subtypes of bladder cancer.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - year:2024

Enthalten in:

Molecular oncology - (2024) vom: 02. März

Sprache:

Englisch

Beteiligte Personen:

Lammert, Franziska C [VerfasserIn]
Pannhausen, Julia [VerfasserIn]
Noetzel, Erik [VerfasserIn]
Friedland, Florian [VerfasserIn]
Wirtz, Julia [VerfasserIn]
Herfs, Yannick [VerfasserIn]
Leypold, Sophie [VerfasserIn]
Gan, Lin [VerfasserIn]
Weiskirchen, Ralf [VerfasserIn]
Schnitzler, Tician [VerfasserIn]
Knüchel, Ruth [VerfasserIn]
Maurer, Jochen [VerfasserIn]
Jonigk, Danny D [VerfasserIn]
Rose, Michael [VerfasserIn]
Gaisa, Nadine T [VerfasserIn]

Links:

Volltext

Themen:

Bladder cancer
GRHL3
Journal Article
Oncogene
RHO GTPase
Squamous cell carcinoma
Tumor suppressor gene

Anmerkungen:

Date Revised 02.03.2024

published: Print-Electronic

Citation Status Publisher

doi:

10.1002/1878-0261.13623

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369198484