YAP promotes global mRNA translation to fuel oncogenic growth despite starvation
Autor: | Daehee Hwang, Seonguk Baek, Jeeyoon Chang, Taejun Seol, Bomin Ku, Hongseok Ha, Hyeonji Lee, Suhyeon Cho, Tae-Young Roh, Yoon Ki Kim, Dae-Sik Lim |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2024 |
Předmět: | |
Zdroj: | Experimental and Molecular Medicine, Vol 56, Iss 10, Pp 2202-2215 (2024) |
Druh dokumentu: | article |
ISSN: | 2092-6413 05047668 |
DOI: | 10.1038/s12276-024-01316-w |
Popis: | Abstract Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) play fundamental roles in stem/progenitor cell expansion during homeostasis, and their dysregulation often leads to tissue overgrowth. Here, we show that YAP activation is sufficient to overcome the restriction of global protein synthesis induced by serum starvation, enabling cells to sustain proliferation and survival despite an unfavorable environment. Mechanistically, YAP/TAZ selectively promoted the mTORC1-dependent translation of mRNAs containing 5′ terminal oligopyrimidine (5′TOP) motifs, ultimately increasing the cellular polysome content. Interestingly, DNA damage-inducible transcript 4 (DDIT4), a negative regulator of mTORC1, was upregulated by serum starvation but repressed by YAP/TAZ. DDIT4 was sufficient to suppress the translation and transformative potential of uveal melanoma cells, which are often serum unresponsive due to G protein mutations. Our findings reveal a vital role for protein synthesis as a key modality of YAP/TAZ-induced oncogenic transformation and indicate the potential for targeting mTORC1 or translation to treat YAP/TAZ-driven malignancies. |
Databáze: | Directory of Open Access Journals |
Externí odkaz: |