The autophagy sensor ITPR1 protects renal carcinoma cells from NK-mediated killing.

摘要: Clear cell renal carcinoma (ccRCC) is dominated by inactivating mutations in VHL (von Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase), leading to constitutive activation of the hypoxia-inducible factors (HIFs) and induction a hypoxia response transcription signature. Our study demonstrated that mutation results acquisition ccRCC resistance NK-mediated lysis mechanism involving EPAS1/HIF-2α stabilization. More importantly we identified ITPR1 (inositol 1,4,5-trisphosphate receptor, type 1) as direct novel target EPAS1 potent regulator killing through autophagy cells signal derived from NK cells. Therefore, it conceivable consider or sensor potential future therapeutic protocols aim improve responses patients with RCC other solid malignancies.