The emerging roles of TLR and cGAS signaling in tumorigenesis and progression of ovarian cancer

Abstract

Ovarian cancer is fatal to women and has a high mortality rate. Although on-going efforts are never stopped in identifying diagnostic and intervention strategies, the disease is so far unable to be well managed. The most important reason for this is the complexity of pathogenesis for OC, and therefore, uncovering the essential molecular biomarkers accompanied with OC progression takes the privilege for OC remission. Inflammation has been reported to participate in the initiation and progression of OC. Both microenvironmental and tumor cell intrinsic inflammatory signals contribute to the malignancy of OC. Inflammation responses can be triggered by various kinds of stimulus, including endogenous damages and exogenous pathogens, which are initially recognized and orchestrated by a series of innate immune system related receptors, especially Toll like receptors, and cyclic GMP-AMP synthase. In this review, we will discuss the roles of innate immune system related receptors, including TLRs and cGAS, and responses both intrinsic and exogenetic in the development and treatment of OC.

High-Grade Serous Ovarian Cancer—A Risk Factor Puzzle and Screening Fugitive

“…The interleukin-1α (IL1A) gene SNP rs17561 was associated with a reduced risk of endometroid, mucinous, and clear-cell ovarian cancers but not HGSOC, indicating the genetic diversity of ovarian epithelial tumors [38]. Toll-like receptors (TLRs) are engaged in the inflammatory pathways, and their activation in ovarian cancer is closely related to cancer aggressiveness, chemo-resistance, and adverse clinical outcomes [39,40]. The interaction between TLR4 and MyD88, the molecule considered to be the marker of stem cells in ovarian cancer, contributes to inflammation in the tumor environment and enhances its aggressive phenotype [41].…”

“…TLRs are engaged in the inflammatory pathways, and their activation in ovarian cancer is closely related to cancer aggressiveness, chemo-resistance, and adverse clinical outcomes. [39,40,42] HLA-DP rs3077 AA, HLA-DQ rs3920 GG, ICAM-1 rs1437 CC, and CT genotypes These genotypes are correlated with an increased risk of ovarian cancer and were found to be different in borderline versus malignant tumors.…”