Department of Biomedical Science, Kulliyyah of Allied Health Sciences, International Islamic University Malaysia, Kuantan, Malaysia.
Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, Bangi, Malaysia.
J Oral Pathol Med. 2020 Oct;49(9):835-841. doi: 10.1111/jop.13014. Epub 2020 Apr 18.
Oral squamous cell carcinoma is associated with many known risk factors including tobacco smoking, chronic alcoholism, poor oral hygiene, unhealthy dietary habits and microbial infection. Previous studies have highlighted Candida albicans host tissue infection as a risk factor in the initiation and progression of oral cancer. C albicans invasion induces several cancerous hallmarks, such as activation of proto-oncogenes, induction of DNA damage and overexpression of inflammatory signalling pathways. However, the molecular mechanisms behind these responses remain unclear. A recently discovered fungal toxin peptide, candidalysin, has been reported as an essential molecule in epithelial damage and host recognition of C albicans infection. Candidalysin has a clear role in inflammasome activation and induction of cell damage. Several inflammatory molecules such as IL-6, IL-17, NLRP3 and GM-CSF have been linked to carcinogenesis. Candidalysin is encoded by the ECE1 gene, which has been linked to virulence factors of C albicans such as adhesion, biofilm formation and filamentation properties. This review discusses the recent epidemiological burden of oral cancer and highlights the significance of the ECE1 gene and the ECE1 protein breakdown product, candidalysin in oral malignancy. The immunological and molecular mechanisms behind oral malignancy induced by inflammation and the role of the toxic fungal peptide candidalysin in oral carcinogenesis are explored. With increasing evidence associating C albicans with oral carcinoma, identifying the possible fungal pathogenicity factors including the role of candidalysin can assist in efforts to understand the link between C albicans infection and carcinogenesis, and pave the way for research into therapeutic potentials.
口腔鳞状细胞癌与许多已知的风险因素有关，包括吸烟、慢性酗酒、口腔卫生不良、不健康的饮食习惯和微生物感染。先前的研究强调了白色念珠菌宿主组织感染是口腔癌发生和发展的一个风险因素。C albicans 的入侵诱导了几种癌变特征，如原癌基因的激活、DNA 损伤的诱导和炎症信号通路的过表达。然而，这些反应背后的分子机制尚不清楚。最近发现的一种真菌毒素肽，念珠菌溶素，被认为是上皮细胞损伤和宿主识别 C albicans 感染的必需分子。念珠菌溶素在炎症小体的激活和诱导细胞损伤中具有明确的作用。几种炎症分子，如 IL-6、IL-17、NLRP3 和 GM-CSF，已与癌症发生有关。念珠菌溶素由 ECE1 基因编码，该基因与 C albicans 的毒力因子有关，如粘附、生物膜形成和丝状形成特性。本综述讨论了口腔癌的最新流行病学负担，并强调了 ECE1 基因和 ECE1 蛋白降解产物念珠菌溶素在口腔恶性肿瘤中的重要性。探讨了炎症引起的口腔恶性肿瘤的免疫学和分子机制，以及毒性真菌肽念珠菌溶素在口腔癌发生中的作用。随着越来越多的证据将 C albicans 与口腔癌联系起来，确定可能的真菌致病性因素，包括念珠菌溶素的作用，可以帮助我们理解 C albicans 感染与癌症发生之间的联系，并为研究治疗潜力铺平道路。
