WNK1 signalling regulates amino acid transport and mTORC1 activity to sustain acute myeloid leukaemia growth.
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Authors
Duan, S
Agger, K
Messling, J-E
Nishimura, K
Han, X
Peña-Rømer, I
Shliaha, P
Damhofer, H
Douglas, M
Kohli, M
Pal, A
Asad, Y
Van Dyke, A
Reilly, R
Köchl, R
Tybulewicz, VLJ
Hendrickson, RC
Raynaud, FI
Gallipoli, P
Poulogiannis, G
Helin, K
Agger, K
Messling, J-E
Nishimura, K
Han, X
Peña-Rømer, I
Shliaha, P
Damhofer, H
Douglas, M
Kohli, M
Pal, A
Asad, Y
Van Dyke, A
Reilly, R
Köchl, R
Tybulewicz, VLJ
Hendrickson, RC
Raynaud, FI
Gallipoli, P
Poulogiannis, G
Helin, K
Document Type
Journal Article
Date
2025-05-27
Date Accepted
2025-05-08
Abstract
The lack of curative therapies for acute myeloid leukaemia (AML) remains an ongoing challenge despite recent advances in the understanding of the molecular basis of the disease. Here we identify the WNK1-OXSR1/STK39 pathway as a previously uncharacterised dependency in AML. We show that genetic depletion and pharmacological inhibition of WNK1 or its downstream phosphorylation targets OXSR1 and STK39 strongly reduce cell proliferation and induce apoptosis in leukaemia cells in vitro and in vivo. Furthermore, we show that the WNK1-OXSR1/STK39 pathway controls mTORC1 signalling via regulating amino acid uptake through a mechanism involving the phosphorylation of amino acid transporters, such as SLC38A2. Our findings underscore an important role of the WNK1-OXSR1/STK39 pathway in regulating amino acid uptake and driving AML progression.
Citation
Nature Communications, 2025, 16 (1), pp. 4920 -
Source Title
Nature Communications
Publisher
NATURE PORTFOLIO
ISSN
2041-1723
eISSN
2041-1723
Collections
Research Team
Telomere Biology
Signalling Cancer Metab
CEO Office
Signalling Cancer Metab
CEO Office