Strikingly, in our 3D organotypic culture system, little α-SMA expression was observed in our normal PF or RF FTMs, and after interaction with the melanoma or HNSCC cell lines, the RFs started to express a much higher level of α-SMA, indicating signaling being activated between the tumor cells and the fibroblasts in the tumor stroma. Here, ACTA1 is linked to head and neck squamous cell carcinoma.