TY - JOUR
T1 - Conclusive Evidence for OCT4 Transcription in Human Cancer Cell Lines
T2 - Possible Role of a Small OCT4-Positive Cancer Cell Population
AU - Miyamoto, Tomoyuki
AU - Mizuno, Nobuhiko
AU - Kosaka, Mitsuko
AU - Fujitani, Yoko
AU - Ohno, Eiji
AU - Ohtsuka, Aiji
N1 - Funding Information:
We wish to thank our laboratory members for helpful support and Editage (www.editage.jp) for English language editing. We are grateful to Shinichi Takeshita for technical assistance with the bioluminescence imaging. This work was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JP23592606 & JP15K15016 to M.K.) and the Translational Research Network Program from the Japan Agency for Medical Research and Development (to M.K.).
Publisher Copyright:
© AlphaMed Press 2018
PY - 2018/9
Y1 - 2018/9
N2 - The role of octamer-binding transcription factor 4 (OCT4) in human cancer is still debated. Although many studies have been published on human OCT4, determining which of the findings are accurate or which are false-positives is currently challenging. We thus developed the most reliable method to date for highly specific and comprehensive detection of genuine OCT4-transcript variants without false-positive results. Our results provided clear evidence that the transcripts of OCT4A, OCT4B, OCT4B1, and other novel splicing variants are indeed present in many cancer cell lines, but are rarely detected in normal tissue-derived differentiated cells. Using the tagged genomic transgene, we then verified endogenous OCT4A translation in cancer cell subpopulations. Moreover, analysis of possible other protein isoforms by enforced expression of OCT4B variants showed that the B164 isoform, designated human OCT4C, is preferentially produced in a cap-dependent manner. We confirmed that the OCT4C isoform, similar to OCT4A, can transform non-tumorigenic fibroblasts in vitro. Finally, ablation of OCT4-positive cells using promoter-driven diphtheria toxin A in high malignant cancer cells caused a significant decrease in migration and Matrigel invasion. These findings strongly suggest a significant contribution of OCT4 to the phenotype of human cancer cells. Stem Cells 2018.
AB - The role of octamer-binding transcription factor 4 (OCT4) in human cancer is still debated. Although many studies have been published on human OCT4, determining which of the findings are accurate or which are false-positives is currently challenging. We thus developed the most reliable method to date for highly specific and comprehensive detection of genuine OCT4-transcript variants without false-positive results. Our results provided clear evidence that the transcripts of OCT4A, OCT4B, OCT4B1, and other novel splicing variants are indeed present in many cancer cell lines, but are rarely detected in normal tissue-derived differentiated cells. Using the tagged genomic transgene, we then verified endogenous OCT4A translation in cancer cell subpopulations. Moreover, analysis of possible other protein isoforms by enforced expression of OCT4B variants showed that the B164 isoform, designated human OCT4C, is preferentially produced in a cap-dependent manner. We confirmed that the OCT4C isoform, similar to OCT4A, can transform non-tumorigenic fibroblasts in vitro. Finally, ablation of OCT4-positive cells using promoter-driven diphtheria toxin A in high malignant cancer cells caused a significant decrease in migration and Matrigel invasion. These findings strongly suggest a significant contribution of OCT4 to the phenotype of human cancer cells. Stem Cells 2018.
KW - Cancer
KW - Cancer stem cells
KW - Malignancy
KW - OCT4
KW - Splicing
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U2 - 10.1002/stem.2851
DO - 10.1002/stem.2851
M3 - Article
C2 - 29770522
AN - SCOPUS:85051054594
VL - 36
SP - 1341
EP - 1354
JO - International Journal of Cell Cloning
JF - International Journal of Cell Cloning
SN - 1066-5099
IS - 9
ER -