O-GlcNAcylation in oral squamous cell carcinoma

Tassaporn Kongkaew; Win Pa Pa Aung; Chayarop Supanchart; Anupong Makeudom; Sarawat Langsa-Ard; Thanapat Sastraruji; Ponlatham Chaiyarit; Suttichai Krisanaprakornkit

doi:10.1111/jop.12680

O-GlcNAcylation in oral squamous cell carcinoma

J Oral Pathol Med. 2018 Mar;47(3):260-267. doi: 10.1111/jop.12680. Epub 2018 Jan 30.

Authors

Tassaporn Kongkaew¹, Win Pa Pa Aung², Chayarop Supanchart^{1

2}, Anupong Makeudom², Sarawat Langsa-Ard², Thanapat Sastraruji², Ponlatham Chaiyarit^{3

4}, Suttichai Krisanaprakornkit^{2

5}

Affiliations

¹ Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
² Center of Excellence in Oral and Maxillofacial Biology, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
³ Department of Oral Diagnosis, Faculty of Dentistry, Khon Kaen University, Khon Kaen, Thailand.
⁴ Research Group of Chronic Inflammatory Oral Diseases and Systemic Diseases Associated with Oral Health, Khon Kaen University, Khon Kaen, Thailand.
⁵ Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.

PMID: 29327476
DOI: 10.1111/jop.12680

Abstract

Background: Two post-translational mechanisms commonly demonstrated in various cancers are protein phosphorylation and glycosylation by O-linked β-N-acetylglucosamine (O-GlcNAc). However, only phosphorylation of the epidermal growth factor receptor (EGFR)/Akt pathway has been reported in oral squamous cell carcinoma (OSCC). Therefore, we aimed to determine both post-translational modifications in OSCC tissues and in oral cancer cells compared to normal tissues and oral keratinocytes and to find correlations of these modifications with histological grading.

Methods: Thirty-two OSCC and ten normal formalin-fixed and paraffin-embedded sections were probed with the anti-O-GlcNAc, anti-O-GlcNAc transferase (OGT), anti-phosphorylated-EGFR^tyr1173 , and anti-phosphorylated-Akt^ser473 antibodies following standard immunohistochemistry. The immunohistochemical (IHC) score was determined using the Fromowitz standard. Whole cell lysates of oral cancer cells and normal oral keratinocytes were immunoblotted with the anti-O-GlcNAc antibody.

Results: The median IHC scores of O-GlcNAc or OGT between OSCC and normal tissues were not different, whereas those of phosphorylated-EGFR^tyr1173 and phosphorylated-Akt^ser473 were significantly higher in OSCC than normal tissues (P < .001 and P < .01, respectively). Similarly, expression of O-GlcNAcylated proteins in oral cancer cells and normal oral keratinocytes did not differ. In the OSCC group, the median IHC scores of O-GlcNAc and OGT were significantly lower than those of phosphorylated-EGFR^tyr1173 and phosphorylated-Akt^ser473 (P < .01 and P < .001, respectively). The IHC scores of O-GlcNAc or OGT were not determined to correlate with histological grading.

Conclusion: Unlike other types of cancers, our findings demonstrate that the levels of O-GlcNAcylation are not significantly increased in OSCC tissues or in oral cancer cells and are not associated with the histological grading of OSCC.

Keywords: Akt; O-GlcNAc transferase; O-GlcNAcylation; epidermal growth factor receptor; oral squamous cell carcinoma.

MeSH terms

Adult
Aged
Aged, 80 and over
Carcinoma, Squamous Cell / metabolism*
ErbB Receptors / metabolism
Female
Glycosylation
Humans
Keratinocytes / metabolism
Male
Middle Aged
Mouth Neoplasms / metabolism*
N-Acetylglucosaminyltransferases / metabolism*
Phosphorylation

Substances

N-Acetylglucosaminyltransferases
O-GlcNAc transferase
ErbB Receptors