Inhibition of RAC1 activity in cancer associated fibroblasts favours breast tumour development through IL-1β upregulation

Impacto

Downloads

Downloads per month over past year

Martínez López, Angélica and García Casas, Ana and Bragado Domingo, Paloma and Orimo, Akira and Castañeda-Saucedo, Eduardo and Castillo Lluva, Sonia (2021) Inhibition of RAC1 activity in cancer associated fibroblasts favours breast tumour development through IL-1β upregulation. Cancer Letters, 521 . pp. 14-28. ISSN 0304-3835

[thumbnail of 1-s2.0-S0304383521004031-main.pdf]
Preview
PDF
Creative Commons Attribution Non-commercial No Derivatives.

4MB

Official URL: https://doi.org/10.1016/j.canlet.2021.08.014



Abstract

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..


Item Type:Article
Additional Information:

CRUE-CSIC (Acuerdos Transformativos 2021)

Uncontrolled Keywords:Stromal RAC1, Cancer-associated fibroblasts, Breast cancer, IL-1β
Subjects:Sciences > Chemistry
Sciences > Chemistry > Biochemistry
ID Code:70122
Deposited On:08 Feb 2022 13:50
Last Modified:22 Feb 2022 09:58

Origin of downloads

Repository Staff Only: item control page