Flipping the Switch: Gene Editing Restores a Critical Kidney Cancer Defence

A critical protein known as BAP1 usually acts as a tumour suppressor, maintaining genome stability and overseeing cell death. However, in clear cell renal cell carcinoma (ccRCC), a specific mutation often breaks BAP1, allowing cancer cells to thrive unchecked. Specifically, the Glu31Lys mutation impairs BAP1's ability to repair DNA and maintain stability.

In a recent study, scientists utilised CRISPR-Cas9-mediated adenine base editing to precisely correct this spelling error in KMRC-20 kidney cancer cells. By reverting the mutation to its healthy state, they successfully reactivated BAP1. The result was a dramatic shift in cell behaviour: the cells regained 'anchorage-dependent growth'. Normally, healthy cells self-destruct when they become detached from their neighbours—a process called anoikis. Cancer cells often evade this to spread through the body.

Restoring BAP1 forced the cancer cells to once again respect these boundaries, increasing apoptosis (programmed cell death) when they were not adhered to a surface. Mechanistically, this restoration dialled down the levels of N-cadherin and β-catenin, proteins involved in cell adhesion and survival signalling. These findings highlight a previously unrecognised role for BAP1 in stopping anchorage-independent survival and underscore the immense potential of precise gene editing to reboot the body's natural cancer defences.