LDOC1 suppresses microbe-induced production of il-1β in human normal and cancerous oral cells through the PI3K/AKT/GSK-3β axis

Chia Huei Lee, Pin Feng Hung, Ko Jiunn Liu, Hsuan Lien Chung, Wen Chan Yang, Kai Cheng Hsu, Tsorng Harn Fong, Hsiu Jung Lo, Ya Ping Chen, Ji Rui Yang, Ching Yu Yen

研究成果: 雜誌貢獻文章同行評審

摘要

Poor oral hygiene (POH) is associated with oral squamous cell carcinoma (OSCC). Oral microbes often proliferate due to POH. Array data show that LDOC1 plays a role in immunity against pathogens. We investigated whether LDOC1 regulates the production of oral microbe-induced IL-1β, an oncogenic proinflammatory cytokine in OSCC. We demonstrated the presence of Candida albicans (CA) in 11.3% of OSCC tissues (n = 80). CA and the oral bacterium Fusobacterium nucleatum stimulate higher levels of IL-1β secretion by LDOC1-deficient OSCC cells than by LDOC1-expressing oral cells. CA SC5314 increased OSCC incidence in 4-NQO (a synthetic tobacco carcinogen) and arecoline-cotreated mice. Loss and gain of LDOC1 function significantly increased and decreased, respectively, CA SC5314-induced IL-1β production in oral and OSCC cell lines. Mechanistic studies showed that LDOC1 deficiency increased active phosphorylated Akt upon CA SC5314 stimulation and subsequent inhibitory phosphorylation of GSK-3βS9 by activated Akt. PI3K and Akt inhibitors and expression of the constitutively active mutant GSK-3βS9A significantly reduced the CA SC5314-stimulated IL-1β production in LDOC1-deficient cells. These results indicate that the PI3K/Akt/pGSK-3β signaling pathway contributes to LDOC1-mediated inhibition of oral microbe-induced IL-1β production, suggesting that LDOC1 may determine the pathogenic role of oral microbes in POH-associated OSCC.
原文英語
文章編號3148
頁(從 - 到)1-20
頁數20
期刊Cancers
12
發行號11
DOIs
出版狀態已發佈 - 十一月 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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