Clinical Significance of Porphyromonas gingivalis Enriching Cancer Stem Cells by Inhibiting Programmed Cell Death Factor 4 in Esophageal Squamous Cell Carcinoma

Abstract

Studies have confirmed that the colonization of Porphyromonas gingivalis (Pg) could promote the malignant evolution of esophageal squamous cell carcinoma (ESCC). Since pathogenic microorganisms can promote malignant tumor proliferation by inhibiting programmed cell death factor 4 (PDCD4) and the decrease of PDCD4 activity can enhance the stemness of cancer cells, we here investigated the functional mechanism by which Pg promoted ESCC chemoresistance and malignancy through inhibiting PDCD4 and enriching cancer stem cells (CSCs). The effects of Pg and PDCD4 on CSCs, chemoresistance and malignancy of ESCC cells were evaluated by in vitro studies. The expression of Pg, PDCD4, and ALDH1 in ESCC tissues were detected by IHC, and the correlations between each index and postoperative survival of ESCC patients were analyzed. The results showed that Pg could inhibit PDCD4 expression and lead to CSCs enrichment in ESCC cells. After eliminating Pg, the expression of PDCD4 was upregulated, the percentage of CSCs, chemoresistance and malignancy were decreased. ESCC patients with Pg-positive, PDCD4negative, and ALDH1-positive have a significant shorter survival. This study proved that eliminating Pg and blocking CSCs enrichment caused by decreasing PDCD4 activity may provide a new strategy for ESCC treatment.

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“…After P. gingivalis elimination, PDCD4 expression was upregulated, and the percentage of CSCs, chemoresistance and malignancy were decreased in ESCC. 213 …”

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“…Therefore, elucidating the key molecular targets of P. gingivalis during the initiation and progression of ESCC will provide valuable insights for early diagnosis. Targeted therapy studies have demonstrated that colonization by P. gingivalis suppresses the expression of programmed cell death factor 4, resulting in the accumulation of cancer stem cells within ESCC cells and facilitating malignant progression[ 85 ]. Moreover, prolonged colonization by P. gingivalis results in the upregulation of the inflammatory cytokine glycogen synthetase kinase 3β, which facilitates mitochondrial oxidative phosphorylation (mtOXPHOS) and fosters malignant progression in ESCC[ 86 ].…”