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Kidney cancer

Cracking resistance of RCCs against NK-cell-mediated lysis

Nature Reviews Urology volume 11, page 662 (2014)Cite this article

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Overexpression of inositol 1,4,5-trisphosphate receptor type 1 (ITPR1), mediated by hypoxia-inducible factor 2-α (HIF2-α), protects renal cancer cells from lysis by natural killer (NK) cells through induction of autophagy, according to a new study published in Cancer Research.

First, the team demonstrated that cell lines with mutated VHL constitutively express HIF2-α and are resistant to lysis, but still form stable conjugates with NK cells. When silencing HIF2-α with small interfering RNAs the cells were again susceptible to lysis. Gene expression analysis using DNA microarray technology identified three genes involved in cell death and survival that were downregulated in the absence of HIF2-α expression. In the presence of HIF2-α, direct silencing of one of those genes, ITPR1, restored lysis susceptibility, pointing towards a central role of this gene in the resistance of RCCs with dysfunctional VHL to NK-cell-mediated lysis.

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References

  1. Messai, Y. et al. ITPR1 protects renal cancer cells against natural killer cells by inducing autophagy. Cancer Res. 10.1158/0008-5472.CAN-14-0303

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Authors
  1. Clemens Thoma
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Thoma, C. Cracking resistance of RCCs against NK-cell-mediated lysis. Nat Rev Urol 11, 662 (2014). https://doi.org/10.1038/nrurol.2014.300

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  • DOI: https://doi.org/10.1038/nrurol.2014.300

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