A CAF subcluster regulates bladder cancer stemness

Single-cell RNA sequencing of bladder cancer samples was used to identify a subcluster of cancer-associated fibroblasts (CAFs) overexpressing the urea transporter SLC14A1, which is activated through interferon signalling and stimulates bladder cancer cell stemness. Conversely, interferon derived from the activation of the cGAS–STING pathway in tumor cells was shown to regulate SLC14A1+ CAF differentiation. Furthermore, inhibition of the STING pathway and, in turn, of SLC14A1+ CAFs increased the sensitivity of tumor cells to chemotherapy. These results can have important clinical implications, as patients with bladder cancer with a high percentage of SLC14A1+ CAFs have worse outcomes and responses to therapy.