A systematic CRISPR screen reveals an NBL1-mediated Jak/Stat3 crosstalk to promote ovarian cancer metastasis

TL;DR

This study identifies NBL1 as a key driver of ovarian cancer metastasis through a crosstalk mechanism involving peritoneal cells and the Jak/Stat3 pathway.

Contribution

The paper reveals a novel NBL1-mediated crosstalk mechanism promoting ovarian cancer metastasis.

Findings

NBL1 is significantly upregulated in ovarian cancer patients during peritoneal metastasis.

NBL1 overexpression enhances transcoelomic metastasis in ovarian cancer cells.

NBL1 facilitates crosstalk between peritoneal epithelial and mesothelial cells via Jak/Stat3 activation.

Abstract

Patients with ovarian cancer (OC) are at high risk of developing transcoelomic metastasis in the early stages, which is strongly associated with increased mortality rates. However, the mechanism by which OC cells disseminate from the primary site and colonize distant sites remains unknown. Here, through an in vivo genome-wide CRISPR/Cas9 screen, we identified NBL1, which increased dramatically in OC patients during peritoneal metastasis, as a key factor promoting the transcoelomic metastasis of OC. Overexpression of NBL1 in OC cells greatly promotes the transcoelomic metastasis. When OC cells disseminate into the peritoneal cavity, they induce the transition of peritoneal epithelial cells to mesothelial cells, ultimately activating the Jak/Stat3 signaling pathway. Thus, we show a NBL1-mediated crosstalk between peritoneum epithelial cells and mesothelial cells that supports a metastasis-promoting process.

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