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

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

Cancer letters (2021-08-23)
Angélica Martínez-López, Ana García-Casas, Paloma Bragado, Akira Orimo, Eduardo Castañeda-Saucedo, Sonia Castillo-Lluva
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.

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