DPYSL2 interacts with JAK1 to mediate breast cancer cell migration

Areej Abu Rmaileh, Balakrishnan Solaimuthu, Anees Khatib, Shirel Lavi, Mayur Tanna, Arata Hayashi, Michal Ben Yosef, Michal Lichtenstein, Nir Pillar, Yoav D. Shaul*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageAmerican English
Article numbere202106078
JournalJournal of Cell Biology
Volume221
Issue number7
DOIs
StatePublished - 4 Jul 2022

Bibliographical note

Publisher Copyright:
© 2022 Abu Rmaileh et al.

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