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Oncogenes

Altered traffic flow

Nature Reviews Cancer volume 15, page 574 (2015)Cite this article

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Using an RNA interference screen in HeLa cells, Wheeler et al. found that the small GTPase RAB35 is a regulator of PI3K signalling. Several RAB proteins, which are known to regulate endomembrane trafficking, were identified in the screen. Further study of RAB35 — which has been reported to be mutated in human cancers — confirmed that RAB35 loss in several cell lines suppressed phosphorylation of AKT, indicating that RAB35 is a positive regulator of PI3K signalling. Furthermore, activated RAB35 was sufficient to stimulate PI3K–AKT signalling and altered the localization of platelet-derived growth factor receptor-α (PDGFRα) to lysosomal-associated membrane protein 2 (LAMP2)-positive endomembranes. Analysis of two cancer-associated somatic mutations previously reported in RAB35 indicated that these constitutively activate PI3K–AKT signalling and transform cells. However, whether the tumour-associated RAB35 mutants also alter PDGFRα trafficking or have another mechanism of action is unknown.

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References

  1. Wheeler, D. B. et al. Identification of an oncogenic RAB protein. Science http://dx.doi.org/10.1126/science.aaa4903 (2015)

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  1. Sarah Seton-Rogers
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Seton-Rogers, S. Altered traffic flow. Nat Rev Cancer 15, 574 (2015). https://doi.org/10.1038/nrc4021

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