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

Title
High aldehyde dehydrogenase activity enhances stem cell features in breast cancer cells by activating hypoxia-inducible factor-2α
Authors
Kim R.-J.Park J.-R.Roh K.-J.Choi A.-R.Kim S.-R.Kim P.-H.Yu J.H.Lee J.W.Ahn S.-H.Gong G.Hwang J.-W.Kang K.-S.Kong G.Sheen Y.Y.Nam J.-S.
Ewha Authors
신윤용
SCOPUS Author ID
신윤용scopus
Issue Date
2013
Journal Title
Cancer Letters
ISSN
0304-3835JCR Link
Citation
vol. 333, no. 1, pp. 18 - 31
Indexed
SCI; SCIE; SCOPUS WOS scopus
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-2α (HIF-2α) was highly dysregulated in ALDH-positive 4T1 cells. We observed that ALDH was highly correlated with the HIF-2α expression in breast cancer cell lines and tissues. DEAB treatment of breast cancer cells reduced the expression of HIF-2α in vitro. In addition, reduction of HIF-2α 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. © 2012 Elsevier Ireland Ltd.
DOI
10.1016/j.canlet.2012.11.026
Appears in Collections:
약학대학 > 약학과 > Journal papers
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