Cell aggregation induces phosphorylation of PECAM-1 and Pyk2 and promotes tumor cell anchorage-independent growth

Molecular Cancer

Research

Qiang Yu¹  Li-hua Xu²  Xing Zhang² 

[1] Department of Pharmacology, Shanghai Institute of Materia Medica, China Academy of Sciences, 555 Zuchongzhi Road, 201203, Shanghai, China;State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Dongfeng East Road, 510060, Guangzhou, China;

关键词: A549 Cell;    Focal Adhesion Kinase;    H460 Cell;    Cell Aggregation;    Soft Agar;   

DOI  :  10.1186/1476-4598-9-7

 received in 2009-07-15, accepted in 2010-01-14,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundApoptosis caused by inadequate or inappropriate cell-matrix interactions is defined as anoikis. Although transformed cells are known to be anoikis-resistant, the underlying mechanisms have not been well understood. We investigated the mechanisms of anoikis resistance of tumor cells.ResultsWe observed that cell aggregation in suspension promoted cell survival and proliferation. We demonstrated a correlation between tumor cell aggregation in suspension and cell growth in soft agar. Analysis of tyrosine kinase-mediated cell survival and growth signaling pathways revealed increased levels of tyrosine-phosphorylation of PECAM-1 and Pyk2 in cell aggregates. We also showed that PECAM-1 and Pyk2 physically interact with each other, and that PECAM-1 carrying a deletion of exons 11-16 could no longer bind to Pyk2. Furthermore, RNA interference-mediated reduction of Pyk2 and PECAM-1 protein levels reduced cell aggregation and inhibited the growth of tumor cells in soft agar.ConclusionsThe data demonstrated that Pyk2 and PECAM-1 were critical mediators of both anchorage-independent growth and anoikis resistance in tumor cells.

【 授权许可】

Unknown   
© Zhang et al; licensee BioMed Central Ltd. 2010. 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.