1. Microbial sensors and responders in colorectal cancer.
Microbial sensors and responders in colorectal cancer. Intestinal epithelial cells and myeloid cells sense microbe-associated molecular patterns (MAMP) through TLR and NLR PRRs. Interaction of MAMPs with cell surface-bound TLRs leads to activation of transcription factor NF-kB via the adaptor molecule MyD88. NF-kB signaling in epithelial cells alters the expression of antiapoptotic genes including Bcl2L1 and Bcl2, contributing to the transformation of epithelial cells. NF-κB activation in the myeloid cells upregulates levels of IL-6 and IL-23, which increase Th17 cells that play a critical role in colitis-associated colorectal cancer. IL-6 can directly contribute to the development of colon cancer through the activation of STAT3. PTGS2 (COX-2) is a key inflammatory mediator in colorectal cancer. Nlrp3 and Nlrp6, members of NLR family sense microbial and non-microbial patterns in the cytosolic compartment and are components of inflammasomes, which function in protection from colorectal cancer.
Aleksandar D. Kostic et al. Cancer Immunol Res 2013;1:
©2013 by American Association for Cancer Research