Molecular analysis of cancer stem cells drived from uterine carcinosarcoma

Research Project

Project/Area Number	26460427
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Human pathology
Research Institution	Kitasato University
Principal Investigator	SAEGUSA Makoto 北里大学, 医学部, 教授 (00265711)
Project Period (FY)	2014-04-01 – 2017-03-31
Project Status	Completed (Fiscal Year 2016)
Budget Amount *help	¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000) Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000) Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000) Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords	子宮癌肉腫 / beta-catenin / Sox / 癌幹細胞 / βーカテニン / Sox4 / Slug / EMT
Outline of Final Research Achievements	Uterine carcinosarcoma (UCS) represents a example of cancer associated with epithelial-mesenchymal transition (EMT), which exhibits cancer stem cell (CSC)-like traits. In this study, Em Ca cells cultured in serum-free medium for mesenchymal stem cells underwent EMT through downregulation of E-cadherin and upregulation of Slug. The cells also showed CSC properties. Overexpression of Sox4 led to transactivation of the Slug promoter, enhancing beta-catenin/p300-mediated transcription of the Slug gene. In clinical samples, both beta-catenin and Slug scores were significantly higher in the sarcomatous as compared to carcinomatous components in UCSs, and were positively correlated with Sox4, Sox7, and Sox9 scores. In conclusion, Sox4, as well as Sox7 and Sox9, may contribute to regulation of EMT/CSC properties to promote development of sarcomatous components in UCSs through transcriptional regulation of the Slug gene by cooperating with the beta-catenin/p300 signal pathway.