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Extracellular vesicles from colorectal cancer cells promote metastasis via the NOD1 signalling pathway.

ABSTRACT: Pattern-recognition receptors (PRRs) have been shown to promote tumour metastasis via sensing tumour cell-derived small extracellular vesicles (EVs). Nucleotide-binding oligomerisation domain 1 (NOD1), a cytoplasmic PRR, plays a role in colorectal cancer (CRC) by detecting bacterial products. However, the precise mechanisms underlying the effects of NOD1, following identification of CRC cell-derived EVs (CRC-EVs), to potentiate CRC liver metastasis (CRC-LM), remain poorly understood. Here, we demonstrate that CRC-EVs activate NOD1 in macrophages to initiate secretion of inflammatory cytokines and chemokines. NOD1-activated macrophages also promote CRC cell migration, while in a murine model of liver metastasis (LM), NOD1-deficient mice exhibit reduced metastasis following CRC-EV treatment. Furthermore, cell division cycle 42 (CDC42), a small Rho guanosine-5'-triphosphate (GTP)ase, is delivered by CRC-EVs into macrophages where it activates NOD1. In addition, EVs from the plasma of patients with CRC-LM mediate NOD1 activation in human peripheral blood mononuclear cells. Moreover, high NOD1 expression in tumour tissues is associated with poor prognosis of CRC-LM. Our findings suggest that CRC-EVs activate NOD1 to promote tumour metastasis, thus, NOD1 may serve as a potential target in the diagnosis and treatment of CRC-LM.

SUBMITTER: Wei X

PROVIDER: S-EPMC9448875 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Extracellular vesicles from colorectal cancer cells promote metastasis via the NOD1 signalling pathway.

Wei Xiduan X Ye Jingjia J Pei Yameng Y Wang Chunting C Yang Hongzhen H Tian Jingyuan J Si Guangxu G Ma Yao Y Wang Kun K Liu Gang G

Journal of extracellular vesicles 20220901 9

Pattern-recognition receptors (PRRs) have been shown to promote tumour metastasis via sensing tumour cell-derived small extracellular vesicles (EVs). Nucleotide-binding oligomerisation domain 1 (NOD1), a cytoplasmic PRR, plays a role in colorectal cancer (CRC) by detecting bacterial products. However, the precise mechanisms underlying the effects of NOD1, following identification of CRC cell-derived EVs (CRC-EVs), to potentiate CRC liver metastasis (CRC-LM), remain poorly understood. Here, we de ...[more]

PMID: 36068649

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Extracellular vesicles from colorectal cancer cells promote metastasis via the NOD1 signalling pathway.

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Extracellular vesicles from colorectal cancer cells promote metastasis via the NOD1 signalling pathway.

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