RhoC regulates cancer stem cells in head and neck squamous cell carcinoma by overexpressing IL-6 and phosphorylation of STAT3

Autor: Smita Sharma, Theodoros N. Teknos, Mozaffarul Islam
Jazyk: angličtina
Rok vydání: 2014
Předmět:
rho GTP-Binding Proteins
RhoC
lcsh:Medicine
Signal transduction
Molecular cell biology
Phosphorylation
RNA
Small Interfering
lcsh:Science
Gene knockdown
Multidisciplinary
biology
Flow Cytometry
Head and Neck Tumors
Gene Expression Regulation
Neoplastic
Isoenzymes
Hyaluronan Receptors
Oncology
Head and Neck Neoplasms
rhoC GTP-Binding Protein
Carcinoma
Squamous Cell
Neoplastic Stem Cells
Medicine
Guanosine Triphosphate
Stem cell
Research Article
Homeobox protein NANOG
STAT3 Transcription Factor
Signaling in cellular processes
Aldehyde Dehydrogenase 1 Family
Head and Neck Squamous Cell Carcinoma
SOX2
Cancer stem cell
Cell Line
Tumor
medicine
Humans
Immunoassays
Biology
STAT signaling family
Interleukin-6
CD44
lcsh:R
Cancers and Neoplasms
Retinal Dehydrogenase
medicine.disease
Head and neck squamous-cell carcinoma
Otorhinolaryngology
biology.protein
Cancer research
Immunologic Techniques
Clinical Immunology
lcsh:Q
Cytometry
Transcription Factors
Zdroj: PLoS ONE, Vol 9, Iss 2, p e88527 (2014)
PLoS ONE
ISSN: 1932-6203
Popis: In this study we investigated the correlation between RhoC expression and cancer stem cells (CSCs) formation in head and neck squamous cell carcinoma (HNSCC). The inhibition of RhoC function was achieved using shRNA. The expression of stem cell surface markers, ALDH and CD44 were significantly low in two RhoC depleted HNSCC cell carcinoma cell lines. Furthermore, a striking reduction in tumorsphere formation was achieved in RhoC knockdown lines. The mRNA expression of RhoC in RhoC knockdown adherent and tumorspheres are dramatically down regulated as compared with the scrambled control. The mRNA expression of stem cell transcription factors; nanog, oct3/4 (Pouf1), and sox2 were significantly depleted in RhoC knockdown clones. Further, the phosphorylation of STAT3(ser727), and STAT3(tyr705) were significantly down regulated in RhoC knockdown clones. The overexpression of STAT3 in RhoC knockdown did not show any change in expression patterns of either-STAT3(tyr705) or stem cell transcription factors, signifying the role of RhoC in STAT3 activation and thus the expression of nanog, oct3/4 and sox2 in HNSCC. The expression of Inter leukin-6 (IL-6) in RhoC knockdown HNSCC cell lines was dramatically low as compared to the scrambled control. Further, we have shown a rescue in STAT3 phosphorylation by IL-6 stimulation in RhoC knockdown lines. This study is the first of its kind to establish the involvement of RhoC in STAT3 phosphorylation and hence in promoting the activation of core cancer stem cells (CSCs) transcription factors. These findings suggest that RhoC may be a novel target for HNSCC therapy.
Databáze: OpenAIRE
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