Interactions between tumor cells and the extracellular matrix (ECM) provide both pro-and anti-tumorigenic stimuli and guide the development of cancer. Fibrinogen-a (FGA)-a subunit of the ECM protein Fibrinogen-has recently come under scrutiny as a key anti-tumorigenic factor, but the underlying mechanism is not yet understood. Here, Wang and colleagues employ CRISPR/Cas9 genome editing to ablate FGA from lung cancer cell lines, showing subsequent enhancement of cell migration and colony

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... n, with a corresponding increase in mesenchymal features. Mechanistically, the authors demonstrate that FGA interacts with integrin a5, and that this interaction is critical to control AKT-mTOR signaling in lung cancer cells. Supplementation of FGA into the growth medium, or co-culturing FGA-knockout cells with FGA-replete cells, resulted in restoration of the fibrinogen-integrin signaling pathway in FGA-knockout cells and suppression of cell growth and migration. Overall, the data support a key role for FGA in controlling tumor progression in the lung.