Abstract 2108: Imatinib-induced downregulation of Skp2 inhibits cell growth in human squamous cell carcinoma

Abstract

Abstract It is apparent that Skp2(S-phase kinase associated protein) plays a crucial role in tumorigenesis of various human cancers. Imatinib, inhibitor of BCR-ABL tyrosine kinase, KIT and PDGF receptor, has been approved for the treatment and investigation of chronic myeloid leukemia, gastrointestinal stromal tumors and additional various solid tumors. But An area of skin cancer has not been yet investigated. The aim of this study was to explore the role of the Skp2 in Imatinib antitumor effect on human skin cancer. To explore Imatinib effect on growth of A431 cells (squamous cell carcinoma / skin cancer) we conducted CCK8 assay and Flow cytometry. Western blot assay was performed for determining the functions and molecular mechanism of Imatinib in A431 cells. we found that Imatinib significantly inhibited cell growth and induced cell cycle arrest at G0/G1 phase. Furthermore, we observed that depletion of Skp2 triggered cell cycle arrest and colony formation inhibition by Imatinib. Mechanistically we identified that Imatinib markedly downregulated Skp2 protein expression and subsequently upregulated p21 expression via increased protein stability. In conclusion, Imatinib exerts its antitumor activity via inhibition of Skp2 - p21 axis and these findings suggest that targeting Skp2 by Imatinib could be promising therapeutic approach for Squamous cell carcinoma therapy. Note: This abstract was not presented at the meeting. Citation Format: Hyo Jin Jeong. Imatinib-induced downregulation of Skp2 inhibits cell growth in human squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2108. doi:10.1158/1538-7445.AM2017-2108