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Protein kinase casein kinase 2-mediated upregulation of N-cadherin confers anoikis resistance on esophageal carcinoma cells.

Authors
 Hyeonseok Ko  ;  Seongrak Kim  ;  Cheng-Hao Jin  ;  Eunjung Lee  ;  Sunyoung Ham  ;  Jong In Yook  ;  Kunhong Kim 
Citation
 Molecular Cancer Research, Vol.10(8) : 1032-1038, 2012 
Journal Title
 Molecular Cancer Research 
ISSN
 1541-7786 
Issue Date
2012
Abstract
Previously, we reported that high PKCK2 activity could protect cancer cells from death receptor-mediated apoptosis through phosphorylation of procaspase-2. Because anoikis is another form of apoptosis, we asked whether PKCK2 could similarly confer resistance to anoikis on cancer cells. Human esophageal squamous cancer cell lines with high PKCK2 activity (HCE4 and HCE7) were anoikis-resistant, whereas cell lines with low PKCK2 activity (TE2 and TE3) were anoikis-sensitive. Because the cells showed different sensitivity to anoikis, we compared the expression of cell adhesion molecules between anoikis-sensitive TE2 and anoikis-resistant HCE4 cells using cDNA microarray. We found that E-cadherin is expressed only in TE2 cells; whereas N-cadherin is expressed instead of E-cadherin in HCE4 cells. To examine whether PKCK2 activity could determine the type of cadherin expressed, we first increased intracellular PKCK2 activity in TE2 cells by overexpressing the PKCK2α catalytic subunit using lentivirus and found that high PKCK2 activity could switch cadherin expression from type E to N and confer anoikis resistance. Conversely, a decrease in PKCK2 activity in HCE4 cells by knockdown of PKCK2α catalytic subunit using shRNA induced N- to E-cadherin switching and the anoikis-resistant cells became sensitive. In addition, N-cadherin expression correlated with PKB/Akt activation and increased invasiveness. We conclude that high intracellular PKCK2 activity confers anoikis resistance on esophageal cancer cells by inducing E- to N-cadherin switching.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91469
DOI
10.1158/1541-7786.MCR-12-0261
Appears in Collections:
1. Journal Papers (연구논문) > 2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실)
Yonsei Authors
고현석(Ko, Hyeon Seok)
김건홍(Kim, Kun Hong)
김성락(Kim, Seong Rak)
김성호(Jin, Cheng Hao)
육종인(Yook, Jong In)
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