Abstract
Signal transducer and activator of transcription (STAT)-3 lies at the convergence point of key pathways involved in many malignancies including oral squamous cell carcinoma (OSCC). Endoplasmic reticulum stress (ERS) and the unfolded protein response have been shown to be involved in the pathogenesis and progression of different cancers by influencing key cellular processes such as apoptosis. We investigated the differential expression of STAT3 pathway-related genes and proteins under ERS in OSCC.
MethodsThree normal oral keratinocyte (NOK) and three OSCC cell lines were subjected to tunicamycin to induce ERS for 24 h or to the vehicle medium as control. A pathway-focussed array was used to analyse the modulation of STAT3 pathway gene expression under ERS using qPCR. The expression of key regulated proteins was investigated in the cell lines using immunocytochemistry and in 76 OSCC and 9 normal oral mucosa (NOM) tissue samples using tissue microarray technology and immunohistochemistry.
ResultsERS resulted in up-regulation of interleukin-6 receptor (IL6R) gene in NOK cell lines (p = 0.001) and IL5 (p = 0.005) and IL22 (p = 0.024) in OSCC cell lines. Greater STAT3 (p = 0.019) and leukaemia inhibitory factor receptor (p = 0.042) protein expression was observed in treated than untreated NOK cell lines.
ConclusionsThe gene and protein regulation patterns show that ERS plays a role in modifying the tumour microenvironment in OSCC by up-regulating tumour-promoting cytokines.
Original language | English |
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Pages (from-to) | 130-143 |
Number of pages | 15 |
Journal | Cytokine |
Volume | 120 |
Early online date | 06 May 2019 |
DOIs | |
Publication status | Published - Aug 2019 |
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Dive into the research topics of 'Tunicamycin-induced endoplasmic reticulum stress up-regulates tumour-promoting cytokines in oral squamous cell carcinoma'. Together they form a unique fingerprint.Prizes
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New Zealand Dental Research Foundation Grant
Yakin, M. (Recipient), 2015
Prize: Award › External award
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New Zealand Dental Research Foundation Grant
Yakin, M. (Recipient), Seo, B. (Recipient) & Rich, A. (Recipient), 2016
Prize: Award › External award
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Sir John Walsh Research Institute Research Symposium Oral Molecular and Immunopathology Session Oral Presentation Prize
Yakin, M. (Recipient), 02 Sept 2016
Prize: External prize