RT Journal Article
T1 Inhibition of RAC1 activity in cancer associated fibroblasts favours breast tumour development through IL-1β upregulation
A1 Martínez López, Angélica
A1 García Casas, Ana
A1 Bragado Domingo, Paloma
A1 Orimo, Akira
A1 Castañeda-Saucedo, Eduardo
A1 Castillo Lluva, Sonia
AB 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..
PB Elsevier
SN 0304-3835
YR 2021
FD 2021-08-19
LK https://hdl.handle.net/20.500.14352/4678
UL https://hdl.handle.net/20.500.14352/4678
LA eng
NO CRUE-CSIC (Acuerdos Transformativos 2021)
NO Ministerio de Ciencia e Innovación (MICINN)
NO Ministerio de Economía y Competitividad (MINECO)/FEDER
DS Docta Complutense
RD 20 ago 2024