Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer.
Aldehyde dehydrogenase 1 (ALDH1) has been considered to be a marker for cancer stem cells. However, the role of ALDH1 in head and neck squamous cell carcinoma (HNSCC) has yet to be determined. In this study, we isolated ALDH1-positive cells from HNSCC patients and showed that these HNSCC-ALDH1+ cells displayed radioresistance and represented a reservoir for generating tumors. Based on microarray findings, the results of Western blotting and immunofluorescent assays further confirmed that ALDH1+-lineage cells showed evidence of having epithelial-mesenchymal transition (EMT) shifting and endogenously co-expressed Snail. Furthermore, the knockdown of Snail expression significantly decreased the expression of ALDH1, inhibited cancer stem-like properties, and blocked the tumorigenic abilities of CD44+CD24(-)ALDH1+ cells. Finally, in a xenotransplanted tumorigenicity study, we confirmed that the treatment effect of chemoradiotherapy for ALDH1+ could be improved by Snail siRNA. In summary, it is likely that ALDH1 is a specific marker for the cancer stem-like cells of HNSCC.
Chen
Yu-Chih
YC
Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taiwan.
Chen
Yi-Wei
YW
Hsu
Han-Shui
HS
Tseng
Ling-Ming
LM
Huang
Pin-I
PI
Lu
Kai-Hsi
KH
Chen
Dow-Tien
DT
Tai
Lung-Kuo
LK
Yung
Ming-Chi
MC
Chang
Shih-Ching
SC
Ku
Hung-Hai
HH
Chiou
Shih-Hwa
SH
Lo
Wen-Liang
WL
D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology*; D005260:Female; D055785:Gene Knockdown Techniques; D006258:Head and Neck Neoplasms / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D059630:Mesenchymal Stem Cells / Q000201:enzymology*; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000201:enzymology*; D020411:Oligonucleotide Array Sequence Analysis; D050697:Retinal Dehydrogenase; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D007527:Isoenzymes; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase