Induced Pluripotent-stem-cell Related Genes Contribute to De-differentiation in Oral Squamous Cell Carcinoma.
Cancer stem cells are suspected to contribute to malignancy in tumors. Hypoxia affects cell differentiation and induces stem-cell-like characteristics in malignancies. Induced pluripotency was demonstrated in mouse fibroblasts by reprogramming with four transcriptional factors: Oct3/4, Sox2, c-Myc, and Klf4. Conversely, oncogenic transformations frequently express transcriptional factors and Nanog. Therefore, cancer cells present some similarities with induced pluripotent stem (iPS) cells.



We investigated the expression of iPS-related genes in vitro and in clinical samples to identify their relationships with hypoxia and tumorigenesis.



Oral squamous cell carcinoma (SCC) cells were used to show that expression levels of Oct3/4, Sox2, and Nanog were significantly increased in hypoxic condition in vitro and in moderately- and poorly-differentiated samples.



We propose that Oct3/4, Sox2 and Nanog are associated with tumor hypoxia characterized in oral SCC and that these factors may also contribute to the undifferentiated potency observed in oral SCC clinically.
Departments of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Daisuke
D
Takeda
Departments of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan hasetaku@med.kobe-u.ac.jp.
Takumi
T
Hasegawa
Departments of Rehabilitation Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Takeshi
T
Ueha
Departments of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Eiji
E
Iwata
Departments of Rehabilitation Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Risa
R
Harada
Departments of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Akiko
A
Sakakibara
Departments of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Teruya
T
Kawamoto
Departments of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Tsutomu
T
Minamikawa
Departments of Rehabilitation Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Yoshitada
Y
Sakai
Departments of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Takahide
T
Komori
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D063646:Carcinogenesis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D000090062:Kruppel-Like Factor 4; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D000071317:Nanog Homeobox Protein / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D011379:Prognosis; D055748:SOXB1 Transcription Factors / Q000378:metabolism
C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors
Squamous cell carcinoma; iPS-related genes; induced pluripotent stem cell; reprogramming factors; stemness factors