An MST4‐pβ‐CateninThr40 Signaling Axis Controls Intestinal Stem Cell and Tumorigenesis Article Swipe
Hui Zhang
,
Moubin Lin
,
Chao Dong
,
Yang Tang
,
Liwei An
,
Junyi Ju
,
Fuping Wen
,
Fan Chen
,
Meng Wang
,
Wenjia Wang
,
Min Chen
,
Yun Zhao
,
Jixi Li
,
Steven X. Hou
,
Xinhua Lin
,
Lulu Hu
,
Wenbo Bu
,
Dianqing Wu
,
Lin Li
,
Shi Jiao
,
Zhaocai Zhou
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1002/advs.202004850
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1002/advs.202004850
Elevated Wnt/ β ‐catenin signaling has been commonly associated with tumorigenesis especially colorectal cancer (CRC). Here, an MST4‐p β ‐catenin Thr40 signaling axis essential for intestinal stem cell (ISC) homeostasis and CRC development is uncovered. In response to Wnt3a stimulation, the kinase MST4 directly phosphorylates β ‐catenin at Thr40 to block its Ser33 phosphorylation by GSK3 β . Thus, MST4 mediates an active process that prevents β ‐catenin from binding to and being degraded by β ‐TrCP, leading to accumulation and full activation of β ‐catenin. Depletion of MST4 causes loss of ISCs and inhibits CRC growth. Mice bearing either MST4 T178E mutation with constitutive kinase activity or β ‐catenin T40D mutation mimicking MST4‐mediated phosphorylation show overly increased ISCs/CSCs and exacerbates CRC. Furthermore, the MST4‐p β ‐catenin Thr40 axis is upregulated and correlated with poor prognosis of human CRC. Collectively, this work establishes a previously undefined machinery for β ‐catenin activation, and further reveals its function in stem cell and tumor biology, opening new opportunities for targeted therapy of CRC.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/advs.202004850
- OA Status
- gold
- Cited By
- 22
- References
- 82
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3179746261
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3179746261Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1002/advs.202004850Digital Object Identifier
- Title
-
An MST4‐pβ‐CateninThr40 Signaling Axis Controls Intestinal Stem Cell and TumorigenesisWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-07-08Full publication date if available
- Authors
-
Hui Zhang, Moubin Lin, Chao Dong, Yang Tang, Liwei An, Junyi Ju, Fuping Wen, Fan Chen, Meng Wang, Wenjia Wang, Min Chen, Yun Zhao, Jixi Li, Steven X. Hou, Xinhua Lin, Lulu Hu, Wenbo Bu, Dianqing Wu, Lin Li, Shi Jiao, Zhaocai ZhouList of authors in order
- Landing page
-
https://doi.org/10.1002/advs.202004850Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1002/advs.202004850Direct OA link when available
- Concepts
-
Wnt signaling pathway, Stem cell, Cancer research, Beta-catenin, Cell biology, Carcinogenesis, Catenin, Biology, Signal transduction, Cancer stem cell, Cancer, GeneticsTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
22Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 4, 2024: 2, 2023: 11, 2022: 4, 2021: 1Per-year citation counts (last 5 years)
- References (count)
-
82Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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