Zhiqiang, Guo; Bergeron, Karl-Frédérik et Mounier, Catherine
(2024).
« Oleate Promotes Triple Negative Breast Cancer Cell Migration by Enhancing Filopodia Formation in a PLD2/Cdc42-dependent Pathway ».
International Journal of Molecular Sciences, 25.
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Résumé
Breast cancer, particularly triple-negative breast cancer (TNBC), poses a formidable global health challenge. Emerging evidence has established a positive association between elevated levels of stearoyl-CoA desaturase 1 (SCD1) and oleic acid (OA) with cancer initiation and metastasis. Our recent investigation illuminatedstudy shown the connection between SCD1, OA, and alterations in migration speed, direction, and cell morphology in TNBC cells. Despite these observationsHowever, the intricate molecular mechanisms governing these associations remain elusive. This study demonstrates that OA stimulation induces rapid cell membrane ruffling in TNBC cell lines, accompanied by a pronounced formation of filopodia . Furthermore, OA treatment triggers the translocation of Cdc42 and Arp2 , indicating their activation. Notably, inhibiting Cdc42, but not Arp2/3 complex, effectively abolishes OA-induced filopodia formation and impedes cell migration. Additionally, we identifiedshowed that phospholipase D2 (PLD2) as a crucial player inworks upstream of Cdc42-dependent filopodia signalingformation and cell migration. Bioinformatic analysis revealed that elevated Cdc42 expression in TNBC, correlating with a lower survival rate in patients. In conclusion, our findings underscore that OA promotes TNBC cell migration by augmenting increasing filopodia formation through a PLD2/Cdc42 pathway. This insight unveils a potential avenue for novel therapeutic strategies in the treatment of TNBC.
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