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Lung cancer

A regulator of senescence

Nature Reviews Cancer volume 10, pages 814–815 (2010)Cite this article

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Vicent and colleagues used a series of negative selection RNA interference (RNAi) screens in vitro and in vivo and identified three genes — Rac1, Phb2 and Wt1 — that are required for Kras-driven oncogenesis. They focused on the role of Wt1 in Kras-driven tumorigenesis, as WT1 had previously been identified as a transcriptional regulator of the Kras gene expression signature. The authors examined the effects of mutant oncogenic Kras (KrasG12D/+) and KrasG12D/+;Wt1Δ/Δ in mouse embryonic fibroblasts (MEFs) and found that KrasG12D/+ cells were hyperproliferative, whereas KrasG12D/+;Wt1Δ/Δ cells showed reduced proliferation. Loss of Wt1 in the context of wild-type Kras had no effect on MEF proliferation, suggesting the cell cycle effects depend on an interaction between oncogenic Kras and Wt1. Moreover, KrasG12D/+;Wt1Δ/Δ MEFs showed characteristics of senescence — they had a flattened morphology, stained positive for senescence-associated β-galactosidase and showed increased localization of promyelocytic leukaemia protein to nuclear bodies.

Wt1 is important for both tumour initiation and tumour progression in the context of oncogenic Kras.

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ORIGINAL RESEARCH PAPER

  1. Vicent, S. et al. Wilms tumor 1 (WT1) regulates KRAS-driven oncogenesis and senescence in mouse and human models. J. Clin. Invest. 120, 3940–3952 (2010)

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  1. Meera Swami
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Swami, M. A regulator of senescence. Nat Rev Cancer 10, 814–815 (2010). https://doi.org/10.1038/nrc2972

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