YAP/TAZ drives cell proliferation and tumour growth via a polyamine-eIF5A hypusination-LSD1 axis (RNA-Seq)

ABSTRACT: Here using mouse genetic models and human cancer cells, we show that YAP/TAZ reprogram polyamine metabolism to promote cell proliferation and tumor growth. Mechanistically, YAP/TAZ increases polyamine synthesis mainly through direct upregulation of the major rate-limiting enzyme ornithine decarboxylase 1. We further demonstrate that the polyamine spermidine sustains eukaryotic translation factor 5A (eIF5A) hypusination to support efficient translation of histone demethylase LSD1 that maintains a favored epigenetic status for YAP/TAZ-induced cell proliferation. Furthermore, inhibiting either polyamine synthesis or LSD1 can suppress YAP/TAZ-induced cell proliferation in mouse liver and human cancer cells. Thus our study identifies a YAP/TAZ-polyamine-eIF5A hypusination-LSD1 axis as required for YAP/TAZ-induced cell proliferation and tumor growth and suggests LSD1 as a critical target of polyamine in tumorigenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE176329 | GEO | 2022/01/01

REPOSITORIES: GEO