Person:
Bragado Domingo, Paloma

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First Name
Paloma
Last Name
Bragado Domingo
URI
https://hdl.handle.net/20.500.14352/77645
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
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Author: García Casas, Ana × End date: 2021 × Start date: 2020 × Has files: true × Subject: 577.1 ×

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    Inhibition of RAC1 activity in cancer associated fibroblasts favours breast tumour development through IL-1β upregulation
    (Cancer Letters, 2021) Martínez López, Angélica; García Casas, Ana; Bragado Domingo, Paloma; Orimo, Akira; Castañeda-Saucedo, Eduardo; Castillo Lluva, Sonia
    Cancer-associated fibroblasts (CAFs) are highly abundant stromal components in the tumour microenvironment. These cells contribute to tumorigenesis and indeed, they have been proposed as a target for anti-cancer therapies. Similarly, targeting the Rho-GTPase RAC1 has also been suggested as a potential therapeutic target in cancer. Here, we show that targeting RAC1 activity, either pharmacologically or by genetic silencing, increases the pro-tumorigenic activity of CAFs by upregulating IL-1β secretion. Moreover, inhibiting RAC1 activity shifts the CAF subtype to a more aggressive phenotype. Thus, as RAC1 suppresses the secretion of IL-1β by CAFs, reducing RAC1 activity in combination with the depletion of this cytokine should be considered as an interesting therapeutic option for breast cancer in which tumour cells retain intact IL-1β signalling..