A LATS2 and ALKBH5 positive feedback loop supports their oncogenic roles Article Swipe
Lei Cao
,
Ruohui Han
,
Yingying Zhao
,
Xiaoyang Qin
,
Qian Li
,
Hui Xiong
,
Yu Kong
,
Ziyi Liu
,
Zexing Li
,
Feng Dong
,
Ting Li
,
Xiujuan Zhao
,
Lei Lei
,
Qian Zhao
,
Dayong Liu
,
Baofeng Wang
,
Xudong Wu
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1016/j.celrep.2024.114032
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1016/j.celrep.2024.114032
N(6)-methyladenosine (m6A) critically regulates RNA dynamics in various biological processes. The m6A demethylase ALKBH5 promotes tumorigenesis of glioblastoma, while the intricate web that orchestrates its regulation remains enigmatic. Here, we discover that cell density affects ALKBH5 subcellular localization and m6A dynamics. Mechanistically, ALKBH5 is phosphorylated by the large tumor suppressor kinase 2 (LATS2), preventing its nuclear export and enhancing protein stability. Furthermore, phosphorylated ALKBH5 reciprocally erases m6A from LATS2 mRNA, thereby stabilizing this transcript. Unexpectedly, LATS2 depletion suppresses glioblastoma stem cell self-renewal independent of yes-associated protein activation. Additionally, deficiency in either LATS2 or ALKBH5 phosphorylation impedes tumor progression in mouse xenograft models. Moreover, high levels of LATS2 expression and ALKBH5 phosphorylation are associated with tumor malignancy in patients with gliomas. Collectively, our study unveils an oncogenic positive feedback loop between LATS2 and ALKBH5, revealing a non-canonical branch of the Hippo pathway for RNA processing and suggesting potential anti-cancer interventions.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.celrep.2024.114032
- http://www.cell.com/article/S2211124724003607/pdf
- OA Status
- gold
- Cited By
- 10
- References
- 71
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4393550962
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4393550962Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1016/j.celrep.2024.114032Digital Object Identifier
- Title
-
A LATS2 and ALKBH5 positive feedback loop supports their oncogenic rolesWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-04-01Full publication date if available
- Authors
-
Lei Cao, Ruohui Han, Yingying Zhao, Xiaoyang Qin, Qian Li, Hui Xiong, Yu Kong, Ziyi Liu, Zexing Li, Feng Dong, Ting Li, Xiujuan Zhao, Lei Lei, Qian Zhao, Dayong Liu, Baofeng Wang, Xudong WuList of authors in order
- Landing page
-
https://doi.org/10.1016/j.celrep.2024.114032Publisher landing page
- PDF URL
-
https://www.cell.com/article/S2211124724003607/pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.cell.com/article/S2211124724003607/pdfDirect OA link when available
- Concepts
-
Loop (graph theory), Positive feedback, Feedback loop, Cell biology, Biology, Cancer research, Chemistry, Computer science, Computer security, Engineering, Mathematics, Combinatorics, Electrical engineeringTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
10Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 6, 2024: 4Per-year citation counts (last 5 years)
- References (count)
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71Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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