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Survival of the sweetest

Nature Reviews Cancer volume 8, pages 484–485 (2008)Cite this article

Using prostate, breast and colon cancer cells the authors demonstrated that small interfering RNA (siRNA)-mediated knockdown of EGFR, but not inhibition of EGFR kinase activity, leads to autophagic cell death. Autophagy can occur when external energy sources are low or unobtainable and, although glucose levels remained constant in cells treated with kinase inhibitors, they were decreased by around 50% in cells transfected with EGFR siRNA.

So, how does EGFR maintain intracellular glucose levels? Data indicate that EGFR expression can alter glucose uptake, and the authors also found that expression of the sodium and glucose cotransporter SGLT1 was undetectable in cells treated with EGFR siRNA compared with controls. Moreover, knockdown of SGLT1 directly mimicked EGFR siRNA-mediated autophagy. Downregulation of SGLT1 in the absence of EGFR could be rescued by inhibiting proteasome activity, implying that SGLT1 is degraded in response to the loss of EGFR expression. Importantly, SGLT1 was found to interact with wild-type and a kinase-deficient EGFR, and SGLT1 levels were preserved in cells transfected with EGFR siRNA and siRNA-resistant wild-type or kinase-deficient EGFR constructs. These findings suggest that EGFR stabilizes SGLT1 independently of its kinase activity.

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References

ORIGINAL RESEARCH PAPER

  1. Weihua, Z. et al. Survival of cancer cells is maintained by EGFR independent of its kinase activity. Cancer Cell 13, 385–393 (2008)

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FURTHER READING

  1. Sharma, S. V., Bell, D. W., Settleman, J. & Haber D. A. Epidermal growth factor receptor mutations in lung cancer. Nature Rev. Cancer 7, 169–181 (2007)

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Authors
  1. Katharine H. Wrighton
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Wrighton, K. Survival of the sweetest. Nat Rev Cancer 8, 484–485 (2008). https://doi.org/10.1038/nrc2424

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