LDOC1 Suppresses Microbe-Induced Production of IL-1β in Human Normal and Cancerous Oral Cells through the PI3K/Akt/GSK-3β Axis

Autor: Ya Ping Chen, Ji Rui Yang, Hsiu Jung Lo, Pin Feng Hung, Wen Chan Yang, Kai Cheng Hsu, Ching Yu Yen, Ko Jiunn Liu, Chia Huei Lee, Tsorng Harn Fong, Hsuan Lien Chung
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cancers
Volume 12
Issue 11
Cancers, Vol 12, Iss 3148, p 3148 (2020)
ISSN: 2072-6694
DOI: 10.3390/cancers12113148
Popis: 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-1&beta
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-1&beta
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-1&beta
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-3&beta
S9 by activated Akt. PI3K and Akt inhibitors and expression of the constitutively active mutant GSK-3&beta
S9A significantly reduced the CA SC5314-stimulated IL-1&beta
production in LDOC1-deficient cells. These results indicate that the PI3K/Akt/pGSK-3&beta
signaling pathway contributes to LDOC1-mediated inhibition of oral microbe-induced IL-1&beta
production, suggesting that LDOC1 may determine the pathogenic role of oral microbes in POH-associated OSCC.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje