Induced Pluripotent-stem-cell Related Genes Contribute to De-differentiation in Oral Squamous Cell Carcinoma

Takeda, Daisuke; Hasegawa, Takumi; Ueha, Takeshi; Iwata, Eiji; Harada, Risa; Sakakibara, Akiko; Kawamoto, Teruya; Minamikawa, Tsutomu; Sakai, Yoshitada; Komori, Takahide

doi:10.21873/anticanres.11419

Cited by 9 publications

(7 citation statements)

References 33 publications

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“…Previous studies were mainly focused on the expression of two transcription factors, OCT4 ( POU5F1 ) and SOX2, which regulate NANOG expression through binding to its promoter. NANOG , OCT4 , and SOX2 mRNA expressions have previously been shown to be significantly higher in samples of moderately and poorly differentiated compared to well-differentiated squamous cell carcinoma [ 13 – 15 ]. Our results are consistent with previous studies that have shown that OCT4 and SOX2 are correlated with NANOG in OSCC.…”

Section: Discussionmentioning

confidence: 99%

“…Our results are consistent with previous studies that have shown that OCT4 and SOX2 are correlated with NANOG in OSCC. Another analyzed transcription factor, KLF4 , has been reported to be associated with both oncogenesis and tumor suppression [ 2 , 13 , 19 ]. OCT4 and SOX2 in cooperation with KLF4 can activate NANOG promoter synergistically [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…OCT4 and SOX2 in cooperation with KLF4 can activate NANOG promoter synergistically [ 18 ]. It has been suggested that KLF4 expression can be used as a poor prognostic factor in head and neck cancer [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that it is important as a prognostic marker [ 9 ]. However, little is known about NANOG expression on an mRNA level using quantitative real-time PCR (qPCR) [ 4 , 11 , 13 – 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Expression of NANOG and Its Regulation in Oral Squamous Cell Carcinoma

Grubelnik

Boštjančič

Groselj

et al. 2020

BioMed Research International

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Background. Results of previous studies suggest that NANOG may be an important prognostic biomarker in oral squamous cell carcinoma (OSCC), but there are contradictory results regarding NANOG expression patterns on mRNA and protein levels, and the mechanisms of its regulation are poorly understood. Our aim was to analyze the expression and diagnostic significance of NANOG in OSCC, and the possible mechanisms of its regulation, i.e., protein regulators on mRNA level (OCT4, SOX2, KLF4, AGR2, and NOTCH1), methylation status, copy number variation, and regulatory miRNAs, miR-145, miR-335, miR-150, miR-34a, miR-128, and miR-27a. Methods. Our study included 120 patients with OSCC. Expression of NANOG protein and mRNA was analyzed using immunohistochemistry and qPCR. Expression of regulatory factors, miRNAs, and copy number variation was performed using qPCR. Methylation status of NANOG promoter was determined using PCR and Sanger sequencing. Results. We detected upregulation of NANOG and OCT4 and downregulation of NOTCH1 and AGR2 mRNA in OSCC with lymph node metastases compared to OSCC without lymph node metastases. We observed a strong positive correlation between mRNAs of NANOG and those of its protein regulators OCT4, SOX2, NOTCH1, AGR2, and KLF4. The expression of NANOG was in positive correlation with the expression of miR-34a. There was also a correlation between T status of OSCC and the expression of miR-335 and miR-150 and a correlation of miR-150 with the N status of T2 OSCC. NANOG promoter methylation and copy number variation were only observed in a small proportion of samples. Conclusions. Our findings confirm the diagnostic significance of NANOG in OSCC and provide information on NANOG expression patterns on both mRNA and protein levels. They also suggest that protein regulators and microRNAs might play a crucial role, whereas methylation of its promoter and copy number variation probably have a minor role in the regulation of NANOG expression in OSCC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Expression of NANOG and Its Regulation in Oral Squamous Cell Carcinoma

Grubelnik

Boštjančič

Groselj

et al. 2020

BioMed Research International

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“…It has also been shown that both moderately and poorly differentiated OSCC cells demonstrate higher expression of NANOG, SOX2, and OCT4 under hypoxic conditions, suggesting that CSCs share some similarities with induced pluripotent stem cells (97). It is increasingly recognized that the tumor microenvironment plays an important role in supporting tumor growth and metastasis, and contributes to tumor heterogeneity (98).…”

Section: Discussionmentioning

confidence: 99%

Cancer Stem Cells in Oral Cavity Squamous Cell Carcinoma: A Review

2017

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Cancer stem cells (CSCs) have been identified in oral cavity squamous cell carcinoma (OCSCC). CSCs possess the ability for perpetual self-renewal and proliferation, producing downstream progenitor cells and cancer cells that drive tumor growth. Studies of many cancer types including OCSCC have identified CSCs using specific markers, but it is still unclear as to where in the stem cell hierarchy these markers fall. This is compounded further by the presence of multiple CSC subtypes within OCSCC, making investigation reliant on the use of multiple markers. This review examines the current knowledge in CSC markers OCT4, SOX2, NANOG, ALDH1, phosphorylated STAT3, CD44, CD24, CD133, and Musashi-1, specifically focusing on their use and validity in OCSCC CSC research and how they may be organized into the CSC hierarchy. OCSCC CSCs also express components of the renin–angiotensin system (RAS), which suggests CSCs may be novel therapeutic targets by modulation of the RAS using existing medications.

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New gold(III) chlorophenyl terpyridine complex: Biomolecular interactions and anticancer activity against human oral squamous cell carcinoma

Radisavljević

Kesić

Ćoćić

et al. 2022

Applied Organom Chemis

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In this work we synthesized new monofunctional gold(III) complex [Au(Cl‐Ph‐tpy)Cl]Cl2 (Cl‐Ph‐tpy = 4′‐[4‐chlorophenyl]‐2,2′:6′, 2″‐terpyridine). This complex was characterized by UV–Vis, NMR, IR, and ESI‐MS spectrometry. The kinetic study of the substitution reactions of the Au‐Cl‐Ph‐tpy complex with biomolecules showed that the rate constants depend on the nature of the entering nucleophile. Based on the calculated values of entropy (∆H≠ > 0) and enthalpy (∆S≠ < 0) the proposed substitution mechanism is associative. Additionally, the relative stability and thermodynamic properties of Au‐Cl‐Ph‐tpy complex were compared with the analogue Au‐tpy complex by the B3LYP/def2‐svp method. DNA/BSA binding studies showed that Au‐Cl‐Ph‐tpy complex interacts with CT DNA through the intercalation and moderately quenches the fluorescence of tryptophan residues in serum albumin (BSA). Molecular docking confirmed results obtained by spectroscopic experiments and suggested site I (subdomain IIA) for binding of Au complex to BSA. We demonstrated that the Au chlorophenyl terpyridine complex possessed significant in vitro cytotoxic activity against human oral squamous carcinoma cells (CAL‐27), induced apoptosis, inhibited proliferation of CAL‐27 cells, and induced cell cycle disturbance. Treatment of CAL‐27 cells with the Au complex enhanced expression of cyclin‐dependent kinase inhibitors p21 and p27, resulting in cell cycle arrest in the G1 phase, reduced the percentage of CAL‐27 cells in S phase and decreased expression of Ki‐67. Additionally, Au complex reduced expression of phosphorylated STAT3 and downstream regulated molecules associated with cancer stemness, NANOG, and Sox2 protein.

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Induced Pluripotent-stem-cell Related Genes Contribute to De-differentiation in Oral Squamous Cell Carcinoma

Abstract: 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.

Cited by 9 publications

References 33 publications

Expression of NANOG and Its Regulation in Oral Squamous Cell Carcinoma

Expression of NANOG and Its Regulation in Oral Squamous Cell Carcinoma

Cancer Stem Cells in Oral Cavity Squamous Cell Carcinoma: A Review

New gold(III) chlorophenyl terpyridine complex: Biomolecular interactions and anticancer activity against human oral squamous cell carcinoma

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