In the present study, we used Chinese hamster ovary (CHO) cells recombinantly expressing human HCA2 receptors (CHO-HCA2), and A431 cells, a human epidermoid carcinoma cell line that endogenously express functional human HCA2 receptors [27], to characterize the regulation of the PI3K/Akt signaling pathway mediated by the human HCA2. Here, HCAR2 is linked to squamous cell carcinoma.