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Cited by 281

The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.

ALDH1A Isozymes are Markers of Human Melanoma Stem Cells and Potential Therapeutic Targets

Open access
Luo, Yuchun, Dallaglio, Katiuscia, Chen, Ying, Robinson, William A., Robinson, Steven E., McCarter, Martin D., Wang, Jianbin, Gonzalez, Rene, Thompson, David C., Norris, David A., Roop, Dennis R., Vasiliou, Vasilis, Fujita, Mayumi·2012·Stem Cells
DOI 10.1002/stem.1193
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Abstract

Although the concept of cancer stem cells (CSCs) is well-accepted for many tumors, the existence of such cells in human melanoma has been the subject of debate. In this study, we demonstrate the existence of human melanoma cells that fulfill the criteria for CSCs (self-renewal and differentiation) by serially xenotransplanting cells into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. These cells possess high aldehyde dehydrogenase (ALDH) activity with ALDH1A1 and ALDH1A3 being the predominant ALDH isozymes. ALDH-positive melanoma cells are more tumorigenic than ALDH-negative cells in both NOD/SCID mice and NSG mice. Biological analyses of the ALDH-positive melanoma cells reveal the ALDH isozymes to be key molecules regulating the function of these cells. Silencing ALDH1A by siRNA or shRNA leads to cell cycle arrest, apoptosis, decreased cell viability in vitro, and reduced tumorigenesis in vivo. ALDH-positive melanoma cells are more resistant to chemotherapeutic agents and silencing ALDH1A by siRNA sensitizes melanoma cells to drug-induced cell death. Furthermore, we, for the first time, examined the molecular signatures of ALDH-positive CSCs from patient-derived tumor specimens. The signatures of melanoma CSCs include retinoic acid (RA)-driven target genes with RA response elements and genes associated with stem cell function. These findings implicate that ALDH isozymes are not only biomarkers of CSCs but also attractive therapeutic targets for human melanoma. Further investigation of these isozymes and genes will enhance our understanding of the molecular mechanisms governing CSCs and reveal new molecular targets for therapeutic intervention of cancer.

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Metadata

Authors
Luo, Y., Dallaglio, K., Chen, Y., Robinson, W. A., Robinson, S. E., McCarter, M. D., Wang, J., Gonzalez, R., Thompson, D. C., Norris, D. A., Roop, D. R., Vasiliou, V., & Fujita, M.
Venue
Stem Cells
Publisher
Oxford University Press (OUP)
Published
2012-09-20
Volume
30
Issue
10
Pages
2100-2113
ISSN
  • 1066-5099 (ISSN-L)
  • 1549-4918
DOI
10.1002/stem.1193
OpenAlex
W1958877028
Cited by
281
References
52
FWCI
10.37
Type
journal article
Language
en
Open access
bronze

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