An In Vivo CRISPR Screen Identifies Stepwise Genetic Dependencies of Metastatic Progression.

ABSTRACT: Blood-borne metastasis of breast cancer involves a series of tightly regulated sequential steps, including the growth of a primary tumor lesion, intravasation of circulating tumor cells (CTC), and adaptation in various distant metastatic sites. The genes orchestrating each of these steps are poorly understood in physiologically relevant contexts, owing to the rarity of experimental models that faithfully recapitulate the biology, growth kinetics, and tropism of human breast cancer. Here, we conducted an in vivo loss-of-function CRISPR screen in newly derived CTC xenografts, unique in their ability to spontaneously mirror the human disease, and identified specific genetic dependencies for each step of the metastatic process. Validation experiments revealed sensitivities to inhibitors that a

SUBMITTER: Scheidmann MC 

PROVIDER: S-EPMC7612409 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature