Cyr61/CCN1 signaling is critical for epithelial-mesenchymal transition and stemness and promotes pancreatic carcinogenesis

Molecular Cancer

Research

Inamul Haque¹  Snigdha Banerjee¹  Monami Majumder¹  Peter J Van Veldhuizen¹  Kakali Dhar¹  Smita Mehta¹  Archana De¹  Sushanta K Banerjee²  Douglas McGregor³ 

[1] Division of Hematology and Oncology, Department of Medicine, Cancer Research Unit, Veterans Affairs Medical Center, Kansas City, MO, USA;Division of Hematology and Oncology, Department of Medicine, Cancer Research Unit, Veterans Affairs Medical Center, Kansas City, MO, USA;Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas, USA;Division of Hematology and Oncology, Department of Medicine, Cancer Research Unit, Veterans Affairs Medical Center, Kansas City, MO, USA;Department of Pathology, University of Kansas Medical Center, Kansas City, Kansas, USA;

关键词: Pancreatic Cancer Cell;    Pancreatic Adenocarcinoma;    Side Population;    Pancreatic Cancer Cell Line;    PDAC Cell;   

DOI  :  10.1186/1476-4598-10-8

 received in 2010-09-21, accepted in 2011-01-13,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundDespite recent advances in outlining the mechanisms involved in pancreatic carcinogenesis, precise molecular pathways and cellular lineage specification remains incompletely understood.ResultsWe show here that Cyr61/CCN1 play a critical role in pancreatic carcinogenesis through the induction of EMT and stemness. Cyr61 mRNA and protein were detected in the early precursor lesions and their expression intensified with disease progression. Cyr61/CCN1 expression was also detected in different pancreatic cancer cell lines. The aggressive cell lines, in which the expressions of mesenchymal/stem cell molecular markers are predominant; exhibit more Cyr61/CCN1 expression. Cyr61 expression is exorbitantly higher in cancer stem/tumor initiating Panc-1-side-population (SP) cells. Upon Cyr61/CCN1 silencing, the aggressive behaviors are reduced by obliterating interlinking pathobiological events such as reversing the EMT, blocking the expression of stem-cell-like traits and inhibiting migration. In contrast, addition of Cyr61 protein in culture medium augments EMT and stemness features in relatively less aggressive BxPC3 pancreatic cancer cells. Using a xenograft model we demonstrated that cyr61/CCN1 silencing in Panc-1-SP cells reverses the stemness features and tumor initiating potency of these cells. Moreover, our results imply a miRNA-based mechanism for the regulation of aggressive behaviors of pancreatic cancer cells by Cyr61/CCN1.ConclusionsIn conclusion, the discovery of the involvement of Cyr61/CCN1 in pancreatic carcinogenesis may represent an important marker for PDAC and suggests Cyr61/CCN1 can be a potential cancer therapeutic target.

【 授权许可】

Unknown   
© Haque et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.