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.

癌症相关成纤维细胞 (CAF) 是肿瘤微环境中高度丰富的基质成分。这些细胞有助于肿瘤发生，事实上，它们已被提议作为抗癌治疗的靶点。同样，靶向 Rho-GTPase RAC1 也被认为是癌症的潜在治疗靶点。在这里，我们表明靶向 RAC1 活性，无论是通过药理学还是通过基因沉默，通过上调 IL-1β 分泌来增加 CAF 的促肿瘤发生活性。此外，抑制 RAC1 活性会使 CAF 亚型转变为更具攻击性的表型。因此，由于 RAC1 抑制 CAF 分泌 IL-1β，因此降低 RAC1 活性并消耗这种细胞因子应被视为治疗乳腺癌的一种有趣的治疗选择，其中肿瘤细胞保留完整的 IL-1β 信号传导。