Non-melanoma skin cancer (NMSC) is characterized by a strong desmoplastic reaction, largely responsible for cancer aggressiveness. Within the tumour microenvironment, cancer-associated fibroblasts (CAFs) play a key role in tumour progression, secretion of extracellular matrix proteins and recruitment of immunosuppressive cells. However, pathways involved in acquisition of CAF phenotype remain unclear. In this issue of EMBO Molecular Medicine, Cangkrama et al describe a new mechanism of fibroblast activation in squamous cell carcinoma. Cancer cell-secreted activin A induces a tumour-promoting phenotype in the fibroblast compartment, with distinct properties compared to TGF-β-activated fibroblasts. Activin A reprograms fibroblasts through transcriptional regulation of mDia2 and reduction of nuclear p53, which favours CAF marker expression, and increases tumour growth and migration. Inhibition of this pathway shows promising results in different models and could offer a new therapeutic strategy in NMSC.

中文翻译：

---

癌症相关的成纤维细胞：激活素A在其弓上增加了另一条弦。

非黑素瘤皮肤癌（NMSC）的特征在于强烈的促增塑反应，这在很大程度上导致了癌症的侵袭。在肿瘤微环境中，与癌症相关的成纤维细胞（CAF）在肿瘤进展，细胞外基质蛋白的分泌和免疫抑制细胞的募集中起关键作用。但是，尚不清楚CAF表型的获得途径。在本期《 EMBO分子医学》中，Cangkrama等人描述了鳞状细胞癌中成纤维细胞活化的新机制。与TGF-β活化的成纤维细胞相比，癌细胞分泌的激活素A可以在成纤维细胞腔中诱导肿瘤促进表型。激活素A通过mDia2的转录调控和核p53的减少来重编程成纤维细胞，这有利于CAF标志物的表达，并增加了肿瘤的生长和迁移。抑制该途径在不同模型中显示出令人鼓舞的结果，并可能为NMSC提供新的治疗策略。