Folliculin Deficient Renal Cancer Cells Show Higher Radiosensitivity Through Autophagic Cell Death

The study investigated the effects of irradiation on folliculin deficient renal cancer cells, which are associated with Birt-Hogg-Dubé syndrome. Using cell lines UOK257 and ACHN-5968 (folliculin deficient) and UOK257-2 and ACHN-sc (folliculin expressing), researchers found that folliculin deficient cells were more radiosensitive due to increased autophagic cell death, not apoptosis. Key regulators included increased Beclin 1 protein levels and an activated MAPK pathway. Inhibiting autophagy increased radioresistance, while combining irradiation with the autophagic inducer rapamycin enhanced radiosensitivity. These findings suggested that targeting autophagy could be a more effective therapeutic approach for folliculin deficient renal cell carcinoma.