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

Yosra Messai, Muhammad Zaeem Noman, Bassam Janji, Meriem Hasmim, Bernard Escudier, Salem Chouaib*

*Corresponding author for this work

    Research output: Contribution to journalArticleResearchpeer-review

    27 Citations (Scopus)

    Abstract

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

    Original languageEnglish
    Pages (from-to)1-7
    Number of pages7
    JournalAutophagy
    Volume2015
    DOIs
    Publication statusPublished - 25 Feb 2015

    Keywords

    • autophagy
    • granzyme B
    • hypoxia-inducible factor-2α
    • ITPR1
    • natural killer
    • renal cell carcinoma

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