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

September 2025 in “ Experimental & Molecular Medicine ”

Soung‐Hoon Lee, Minjeong Kang, Mi Ryung Roh, Kang‐Yell Choi

cutaneous squamous cell carcinoma Wnt/β-catenin signaling cyclin-dependent kinase 1 CDK1 small molecules KY19382 KY19334 CXXC5

Studysummary This study observed that the small molecules KY19382 and KY19334 inhibited cancerous traits in human cutaneous squamous cell carcinoma cells by suppressing the Wnt/β-catenin pathway, indicating their potential as treatments for cancers involving CDK1 overexpression and diseases related to CXXC5 accumulation.

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The study investigates the effects of small molecules KY19382 and KY19334 on cutaneous squamous cell carcinoma (cSCC) by targeting the Wnt/β-catenin signaling pathway. These molecules were found to inhibit the malignant phenotype of cSCC cells by suppressing cyclin-dependent kinase 1 (CDK1) expression, which is typically elevated in cSCC patient samples. The study validated the role of CDK1 in cellular transformation and Wnt/β-catenin pathway activation through CDK1 knockdown experiments. Additionally, these molecules reduced carcinogenesis in a mouse skin model. The findings suggest that KY19382 and KY19334 could be potential therapeutic agents for treating cSCC and other cancers associated with CDK1 overexpression, as well as diseases linked to CXXC5 accumulation.

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Research cited in this study

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research Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis

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This study suggests that the interaction between CXXC5 and Dishevelled is a potential target for promoting hair regrowth and hair follicle formation, offering a new approach to treat hair loss.

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This study found that valproic acid promoted hair re-growth in C3H mice by activating the Wnt/β-catenin pathway, suggesting its potential as a treatment for alopecia.

research Beta-Catenin Activity in the Dermal Papilla Regulates Morphogenesis and Regeneration of Hair

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This study found that in mice, inactivating beta-catenin in the dermal papilla reduces hair follicle progenitor proliferation and disrupts the hair cycle.