Molecular pathways and functional varieties of hemophagocytosis-induced keratinization in oral squamous cell carcinoma cells: from cell death to proliferation and invasion

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K15693
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Osaka Dental University (2016); Niigata University (2015)
• Principal Investigator: SAKU Takashi 大阪歯科大学, 歯学部, 客員教授 (40145264)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 病理学 / 実験腫瘍学 / 口腔扁平上皮癌 / ヘモグロビン誘導 / 角化機序

Outline of Final Research Achievements

We have defined the keratinization of oral squamous cell carcinoma as skin-type orthokeratinization due to keratin 17 expression which never occurs in normal oral mucosa. Such an expression of dyskeratotic keratin 17 was shown to be induced by hemophagacytosis-derived hemoglobin released from erythrocytes and to mediate expressions of OH-1, PAR-2, 14-3-3σ, and YAP. These functional factors contributed to molecular pathways not only for cell death but for cellular proliferation and invasion in oral squamous cell carcinoma. In addition, cell death in oral lichen planus was explained by similar mechanisms starting from hemophagacytosis because hemorrhage often occurred along the epithelial interface, and keratinization-based cellular evaluation was confirmed to be useful in oral cytology to diagnose malignancy. This much functional varieties of phagocytosis-mediated keratinization were never expected, when we formulated our hypothesis that keratinization is initiated by hemophagocytosis.

Free Research Field

口腔病理学