RORγ modulates the extracellular matrix to facilitate hepatocellular carcinoma growth and metastasis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA982719 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24894440.fastq.gz | Fastqsanger.gz | |||
| SRR24894441.fastq.gz | Fastqsanger.gz |
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Project description:Peritoneal metastasis (PM) is diagnosed in almost half of patients with advanced gastric cancer (GCa) and has a very poor prognosis. However, the molecular mechanisms of PM in GCa remain poorly understood. Here, we show that the elevated expression of RAR-related orphan receptor gamma (RORγ) in GCa tumors is a key driver of PM. RORγ drives GCa progression and metastasis by assembling a transcriptional complex with HIF-1α that regulates the expression of HIF-1α targets via recruitment of RNA polymerase II and p300. Mechanistically, RORγ hijacks HIF-1α to disrupt the interaction between HIF-1α and PHD3, leading to decreased HIF-1α hydroxylation, ubiquitylation and increased HIF-1α accumulation, nuclear translocation, and transactivation. RORγ antagonists block tumor growth and PM in multiple xenograft GCa models, and they effectively sensitize GCa tumors to chemotherapy in mice. Thus, our study uncovers a mechanism of RORγ-driven PM and offers a potential therapeutic option against advanced GCa.
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