|Cancer||Cell death||Cell cycle||Cytoskeleton||Exo/endocytosis||Differentiation||Division||Organelles||Signalling||Stem cells||Trafficking|
Low-expression of E-cadherin in leukaemia cells causes loss of homophilic adhesion and promotes cell growth
Qing Rao, Ji‑Ying Wang, Jihong Meng, Kejing Tang, Yanzhong Wang, Min Wang, Haiyan Xing, Zheng Tian and Jianxiang Wang1
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 288 Nanjing Road, Tianjin 300020, Peoples Republic of China
E-cadherin (epithelial cadherin) belongs to the calcium-dependent adhesion molecule superfamily and is implicated in the interactions of haematopoietic progenitors and bone marrow stromal cells. Adhesion capacity to bone marrow stroma was impaired for leukaemia cells, suggesting that a breakdown of adhesive mechanisms governed by an adhesion molecule may exist in leukaemic microenvironment. We previously found that E-cadherin was low expressed in primary acute leukaemia cells compared with normal bone marrow mononuclear cells. In this study, we investigate the functional importance of low E-cadherin expression in leukaemia cell behaviours and investigate its effects in the abnormal interaction of leukaemic cells with stromal cells. After expression of E-cadherin was restored by a demethylating agent in leukaemia cells, E-cadherin-specific adhesion was enhanced. Additionally, siRNA (small interfering RNA)-mediated silencing of E-cadherin in Raji cells resulted in a reduction of cell homophilic adhesion and enhancement of cell proliferation and colony formation. These results suggest that low expression of E-cadherin contributes to the vigorous growth and transforming ability of leukaemic cells.
Key words: cell adhesion, cell growth, E-cadherin, leukaemia, RNA interference
Abbreviations: 5-Aza-CdR, 5-aza-2′-deoxycytidine, E-cadherin, epithelial cadherin, GAPDH, glyceraldehyde-3-phosphate dehydrogenase, MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide, SiCDH1, siRNA specific to CDH1, SiCon, control siRNA, siRNA, small interfering RNA
1To whom correspondence should be addressed (email email@example.com).
Received 17 June 2010/1 December 2010; accepted 14 December 2010
Published as Cell Biology International Immediate Publication 14 December 2010, doi:10.1042/CBI20100456
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