Phase separation of DDX21 promotes colorectal cancer metastasis via MCM5-dependent EMT pathway.

ABSTRACT: RNA binding proteins (RBPs) contributes to cancer progression, but the underlying mechanism reminds unclear. Here, we find that DDX21, a representative RBP, is highly expressed in colorectal cancer (CRC), which leads to CRC cell migration and invasion in vitro, and CRC to liver metastasis and lung metastasis in vivo. This effect of DDX21 on CRC metastasis is correlated to the activation of Epithelial-mesenchymal transition (EMT) pathway. Moreover, we reveal that DDX21 protein is phase separated in vitro and in CRC cells, which controls CRC metastasis. Phase-separated DDX21 highly binds on MCM5 gene locus, which is markedly reduced when phase separation is disrupted by mutations on its intrinsically disordered region (IDR). The impaired metastatic ability of CRC upon DDX21 loss is restored

SUBMITTER: Gao H 

PROVIDER: S-EPMC10202810 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature