Abstract 1986: Determining the signaling pathway of epithelial-IKKα deletion-mediated symbiotic bacterial and fungal infection in carcinogenesis

Abstract

Abstract Bacteria and fungi, two major components of the microbiota, generally share niches and develop both antagonistic and symbiotic relationships, regulating the pathological impacts on the host. The epithelium is where the bacterial-fungal interaction occurs most abundantly, but the relationship between the epithelium, bacteria, and fungi on the pathogenesis, particularly tumorigenesis, is poorly understood. IKKα is one of the crucial factors regulating the homeostasis of squamous epithelial tissues. Recently, our lab has established a mouse model that develops esophageal squamous cell carcinomas associated with IKKα reduction, inflammation and chronic fungal infection. Cladosporium cladosporioides was a major type of fungi identified in this mouse model. Because IKKα deletion in the keratinocytes causes impaired skin barrier, we hypothesized that loss of epithelial IKKα may control fungal colonization through regulating the barrier integrity and inflammation. We generated IKKαf/f mice with inducible K15.Cre (IKKαf/f/K15.Cre) specifically expressed in keratinocytes in hair follicles which is considered as skin stem cells. After deleting IKKα in K15 cells in oral mucosa and skin, IKKαf/f/K15.Cre mice were orally inoculated with Cladosporium cladosporioides. We found that epithelial IKKα deletion increased bacterial colonization in oral mucosa and skin. Moreover, Cladosporium infection further promoted bacterial and fungal colonization in oral cavity and development of skin tumors. Taken together, our data suggest that loss of epithelial IKKα induces the bacterial-fungal symbiosis in oral mucosa, promoting skin tumors. This study will shed light on the importance of the epithelial-bacterial-fungal interaction in the pathogenesis, proposing epithelial IKKα as a novel regulator of the bacterial-fungal interaction. Citation Format: Na-Young Song, Jami Willette-Brown, Feng Zhu, Yinling Hu. Determining the signaling pathway of epithelial-IKKα deletion-mediated symbiotic bacterial and fungal infection in carcinogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1986. doi:10.1158/1538-7445.AM2017-1986