USP36 stabilizes nucleolar Snail1 to promote ribosome biogenesis and cancer cell survival upon ribotoxic stress

Kewei Qin, Shuhan Yu, Yang Liu, Rongtian Guo, Shiya Guo, Junjie Fei, Yuemeng Wang, Kaiyuan Jia, Zhiqiang Xu, Hu Chen, Fengtian Li, Mengmeng Niu, Mu-Shui Dai, Lunzhi Dai, Yang Cao, Yujun Zhang, Zhi-Xiong Jim Xiao () and Yong Yi ()
Additional contact information
Kewei Qin: Sichuan University
Shuhan Yu: Sichuan University
Yang Liu: Sichuan University
Rongtian Guo: Sichuan University
Shiya Guo: Sichuan University
Junjie Fei: Sichuan University
Yuemeng Wang: Sichuan University
Kaiyuan Jia: Sichuan University
Zhiqiang Xu: Sichuan University
Hu Chen: Sichuan University
Fengtian Li: Sichuan University
Mengmeng Niu: Sichuan University
Mu-Shui Dai: Oregon Health & Science University
Lunzhi Dai: Sichuan University
Yang Cao: Sichuan University
Yujun Zhang: Sichuan University
Zhi-Xiong Jim Xiao: Sichuan University
Yong Yi: Sichuan University

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Tumor growth requires elevated ribosome biogenesis. Targeting ribosomes is an important strategy for cancer therapy. The ribosome inhibitor, homoharringtonine (HHT), is used for the clinical treatment of leukemia, yet it is ineffective for the treatment of solid tumors, the reasons for which remain unclear. Here we show that Snail1, a key factor in the regulation of epithelial-to-mesenchymal transition, plays a pivotal role in cellular surveillance response upon ribotoxic stress. Mechanistically, ribotoxic stress activates the JNK-USP36 signaling to stabilize Snail1 in the nucleolus, which facilitates ribosome biogenesis and tumor cell survival. Furthermore, we show that HHT activates the JNK-USP36-Snail1 axis in solid tumor cells, but not in leukemia cells, resulting in solid tumor cell resistance to HHT. Importantly, a combination of HHT with the inhibition of the JNK-USP36-Snail1 axis synergistically inhibits solid tumor growth. Together, this study provides a rationale for targeting the JNK-USP36-Snail1 axis in ribosome inhibition-based solid tumor therapy.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-42257-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42257-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-42257-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().