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High aldehyde dehydrogenase activity enhances stem cell features in breast cancer cells by activating hypoxia-inducible factor-2 alpha

Title
High aldehyde dehydrogenase activity enhances stem cell features in breast cancer cells by activating hypoxia-inducible factor-2 alpha
Author
공구
Keywords
Breast cancer; Cancer stem cell; Aldehyde dehydrogenase; Hypoxia-inducible factor-2 alpha
Issue Date
2013-01
Publisher
ELSEVIER IRELAND LTD, ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND
Citation
CANCER LETTERS, Vol.333, No.1 [2013], p18-31
Abstract
High aldehyde dehydrogenase (ALDH) activity has been recognized as a marker of cancer stem cells (CSCs) in breast cancer. In this study, we examined whether inhibition of ALDH activity suppresses stem-like cell properties in a 4T1 syngeneic mouse model of breast cancer. We found that ALDH-positive 4T1 cells showed stem cell-like properties in vitro and in vivo. Blockade of ALDH activity reduced the growth of CSCs in breast cancer cell lines. Treatment of mice with the ALDH inhibitor diethylaminobenzaldehyde (DEAB) significantly suppressed 4T1 cell metastasis to the lung. Recent evidence suggests that ALDH affects the response of stem cells to hypoxia; therefore, we examined a possible link between ALDH and hypoxia signaling in breast cancer. Hypoxia-inducible factor-2 alpha (HIF-2 alpha) was highly dysregulated in ALDH-positive 4T1 cells. We observed that ALDH was highly correlated with the HIF-2 alpha expression in breast cancer cell lines and tissues. DEAB treatment of breast cancer cells reduced the expression of HIF-2 alpha in vitro. In addition, reduction of HIF-2 alpha expression suppressed in vitro self-renewal ability and in vivo tumor initiation in ALDH-positive 4T1 cells. Therefore, our findings may provide the evidence necessary for exploring a new strategy in the treatment of breast cancer. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
URI
http://www.sciencedirect.com/science/article/pii/S0304383512006738?_rdoc=1&_fmt=high&_origin=gateway&_docanchor=&md5=b8429449ccfc9c30159a5f9aeaa92ffbhttp://hdl.handle.net/20.500.11754/41496
ISSN
0304-3835
DOI
10.1016/j.canlet.2012.11.026
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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