Publication: Detachment-induced E-cadherin expression promotes 3D tumor spheroid formation but inhibits tumor formation and metastasis of lung cancer cells
Issued Date
2017-11-07
Resource Type
ISSN
15221563
03636143
03636143
Other identifier(s)
2-s2.0-85033452553
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Mahidol University
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SCOPUS
Bibliographic Citation
American Journal of Physiology - Cell Physiology. Vol.313, No.5 (2017), C556-C566
Suggested Citation
Phattrakorn Powan, Sudjit Luanpitpong, Xiaoqing He, Yon Rojanasakul, Pithi Chanvorachote Detachment-induced E-cadherin expression promotes 3D tumor spheroid formation but inhibits tumor formation and metastasis of lung cancer cells. American Journal of Physiology - Cell Physiology. Vol.313, No.5 (2017), C556-C566. doi:10.1152/ajpcell.00096.2017 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/41703
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Title
Detachment-induced E-cadherin expression promotes 3D tumor spheroid formation but inhibits tumor formation and metastasis of lung cancer cells
Abstract
© 2017 the American Physiological Society. The epithelial-to-mesenchymal transition is proposed to be a key mechanism responsible for metastasis-related deaths. Similarly, cancer stem cells (CSCs) have been proposed to be a key driver of tumor metastasis. However, the link between the two events and their control mechanisms is unclear. We used a three-dimensional (3D) tumor spheroid assay and other CSCindicating assays to investigate the role of E-cadherin in CSC regulation and its association to epithelial-to-mesenchymal transition in lung cancer cells. Ectopic overexpression and knockdown of E-cadherin were found to promote and retard, respectively, the formation of tumor spheroids in vitro but had opposite effects on tumor formation and metastasis in vivo in a xenograft mouse model. We explored the discrepancy between the in vitro and in vivo results and demonstrated, for the first time, that E-cadherin is required as a component of a major survival pathway under detachment conditions. Downregulation of E-cadherin increased the stemness of lung cancer cells but had an adverse effect on their survival, particularly on non-CSCs. Such downregulation also promoted anoikis resistance and invasiveness of lung cancer cells. These results suggest that anoikis assay could be used as an alternative method for in vitro assessment of CSCs that involves dysregulated adhesion proteins. Our data also suggest that agents that restore E-cadherin expression may be used as therapeutic agents for metastatic cancers.