Fig. 7: Schematic models depicting the differential effects of KY19382 and KY19334 on normal keratinocytes and SCC cells. | Experimental & Molecular Medicine

Fig. 7: Schematic models depicting the differential effects of KY19382 and KY19334 on normal keratinocytes and SCC cells.

From: Novel small molecules downregulate CDK1 expression and inhibit Wnt/β-catenin signaling in cutaneous squamous cell carcinoma by targeting its distinct tumor-specific cellular landscape

Fig. 7

Schematic image representing the mechanism of action of KY19382 and KY19334 in noncancer and cancer cells. Left: in the tissue cells of normal state or noncancer diseases, Wnt/β-catenin signaling is suppressed by cytosolic overexpression of the negative regulator CXXC5. Especially, the normal state in which CXXC5 is increased includes stages requiring homeostasis, such as the late stage of cutaneous wound healing or the regression phase of hair follicle cycling12,19. The specific inhibition of the cytosolic function of CXXC5 by its interaction with Dvl by KY19382 or KY19334 restores the suppressed Wnt/β-catenin signaling. This homeostasis process is similar to the restoration of suppressed Wnt/β-catenin signaling in the disease-status cells by the compounds. This results in the expression of target genes that are important for the regeneration of specific tissue cells, such as EDN1, or are required for various normal cellular functions, such as KRT14. Right: in skin cancer, Wnt/β-catenin signaling is activated by increased CDK1 expression. The activation of Wnt/β-catenin signaling induces the expression of oncogenic genes such as MYC and CCND1. The inhibition of CDK1 by KY19382 or KY19334 results in inactivation of Wnt/β-catenin signaling with repression of c-Myc and cyclin D1.

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