Because of the similar capacity of initiating apoptosis after recognizing and binding the invading pathogens, “that type of proteins” in humans was named NLRs after NB-LRR. Initially, researchers discovered a type of protein in humans with a similar structure and physiological function to plant disease resistance receptors known as nucleotide binding-leucine rich repeats (NB-LRRs). NLRs were discovered at the end of the twentieth century. The Discovery of NLRs and Their Structural Characteristics Due to the few reviews on the effect and mechanism of NOD1 and NOD2 in cancer, we will summarize the structural features of NLRs, including NOD1 and NOD2, as well as their role in carcinogenesis and tumor growth in this review. Although TLRs have been extensively studied for their role in multiple cancers, increasing evidence suggests that NLRs, particularly, NOD1 and NOD2, have a close relationship with cancer cell proliferation, invasion, metastasis, and tumor angiogenesis. TLRs are mainly found on the cell membrane, whereas NLRs are found primarily in the cytoplasm. TLRs and NLRs are important components of PRRs. Innate immunity functions by nonspecifically identifying endogenous and exogenous risk factors via pattern recognition receptors (PPRs). Innate immunity is crucial for resisting internal and external environmental stimuli and maintaining immune homeostasis. This review may help better understand the role of NOD1 and NOD2 in cancer and shed light on NOD1 and NOD2 as potential therapeutic targets for tumor immunotherapy. In this review, we focus on concluding the current research progress on the role of NOD1 and NOD2 in a variety of cancers and discussing the potential reasons for the contradicting role of NOD1 and NOD2 in cancers. Despite numerous studies claiming that NOD1 and NOD2 are linked to tumorigenesis and tumor development, it is still unclear whether NOD1 and NOD2 act as cancer's friends or foes. Previous research has identified NOD1 and NOD2 as key players in inflammatory disease and host-microbial defense. As pattern recognition receptors (PRRs), NOD1 and NOD2 may recognize and bind endogenous damage associated molecular patterns (DAMPs) and external pathogenic associated molecular patterns (PAMPs), directing the activation of inflammatory caspases through engaging the adaptor protein RIP2, which further activates the NF- κB and mitogen-activated protein kinase (MAPK) signaling pathways, thereby mediating host innate immunity and regulating the adaptive immunity. The cytosolic nucleotide binding oligomerization domains 1 and 2 receptors (NOD1 and NOD2) are the most widely investigated NLRs. The nucleotide oligomerization domain (NOD)-like receptors (NLRs) are a group of intracellular proteins that are essential for controlling the host's innate immune response.
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