In:
Journal of Cell Biology, Rockefeller University Press, Vol. 221, No. 7 ( 2022-07-04)
Abstract:
The intricate neuronal wiring during development requires cytoskeletal reorganization orchestrated by signaling cues. Because cytoskeletal remodeling is a hallmark of cell migration, we investigated whether metastatic cancer cells exploit axon guidance proteins to migrate. Indeed, in breast cancer patients, we found a significant correlation between mesenchymal markers and the expression of dihydropyrimidinase-like 2 (DPYSL2), a regulator of cytoskeletal dynamics in growing axons. Strikingly, DPYSL2 knockout in mesenchymal-like breast cancer cells profoundly inhibited cell migration, invasion, stemness features, tumor growth rate, and metastasis. Next, we decoded the molecular mechanism underlying this phenomenon and revealed an interaction between DPYSL2 and Janus kinase 1 (JAK1). This binding is crucial for activating signal transducer and activator of transcription 3 (STAT3) and the subsequent expression of vimentin, the promigratory intermediate filament. These findings identify DPYSL2 as a molecular link between oncogenic signaling pathways and cytoskeletal reorganization in migrating breast cancer cells.
Type of Medium:
Online Resource
ISSN:
0021-9525
,
1540-8140
DOI:
10.1083/jcb.202106078
Language:
English
Publisher:
Rockefeller University Press
Publication Date:
2022
detail.hit.zdb_id:
1421310-2
SSG:
12
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