Inoue H.,1 15 1 Kitasato |
Takahashi H.,1 15 1 Kitasato |
Hashimura M.,1 15 1 Kitasato |
Eshima K.,Kitasato University |
And 3 more authors.
BMC Cancer | Year: 2016
Background: Uterine carcinosarcoma (UCS) represents a true example of cancer associated with epithelial-mesenchymal transition (EMT), which exhibits cancer stem cell (CSC)-like traits. Both Sox and β-catenin signal transductions play key roles in the regulation of EMT/CSC properties, but little is known about their involvement in UCS tumorigenesis. Herein, we focused on the functional roles of the Sox/β-catenin pathway in UCSs. Methods: EMT/CSC tests and transfection experiments were carried out using three endometrial carcinoma (Em Ca) cell lines. Immunohistochemical investigation was also applied for a total of 32 UCSs. Results: Em Ca cells cultured in STK2, a serum-free medium for mesenchymal stem cells, underwent changes in morphology toward an EMT appearance through downregulation of E-cadherin, along with upregulation of Slug, known as a target gene of β-catenin. The cells also showed CSC properties with an increase in the aldehyde dehydrogenase (ALDH) 1high activity population and spheroid formation, as well as upregulation of Sox4, Sox7, and Sox9. Of these Sox factors, overexpression of Sox4 dramatically led to transactivation of the Slug promoter, and the effects were further enhanced by cotransfection of Sox7 or Sox9. Sox4 was also able to promote β-catenin-mediated transcription of the Slug gene through formation of transcriptional complexes with β-catenin and p300, independent of TCF4 status. In clinical samples, both nuclear β-catenin and Slug scores were significantly higher in the sarcomatous elements as compared to carcinomatous components in UCSs, and were positively correlated with Sox4, Sox7, and Sox9 scores. Conclusions: These findings suggested that 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 β-catenin/p300 signal pathway. © 2016 Inoue et al.
Horie R.,1 15 1 Kitasato
Forum on Immunopathological Diseases and Therapeutics | Year: 2013
A typical discrepancy exists between the classification of and treatment strategies for lymphomas. The identification of key molecules in subtypes of lymphomas and the development of molecular targeted strategies will fill this gap. Pathological characteristics might be the consequence of deregulated molecular patterns in lymphomas. Therefore, exploration of addictive molecules based on the pathological classification might be an efficient way to establish molecular targeted therapy for lymphomas. The chromosomal translocation characterizing the subtypes of lymphomas and molecular characteristics for each subtype may suggest a molecular biological approach to identifying addictive molecules to be targeted. This review highlights the potential molecular targets in oncogenic signaling pathways in lymphomas. © 2013 by Begell House, Inc.