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Comment
. 2015 Jun;5(6):581-3.
doi: 10.1158/2159-8290.CD-15-0484.

Two Faces of SIVA

Lois Resnick-Silverman  1 , James J Manfredi  2
Affiliations
Comment

Two Faces of SIVA

Lois Resnick-Silverman et al. Cancer Discov. 2015 Jun.

Abstract

In non-small cell lung cancer cells that contain a mutated KRAS gene, SIVA, a p53 target gene that is critical for apoptosis, is overexpressed in a p53-independent manner and promotes tumorigenesis through the stimulation of mTOR signaling. The ablation of Siva in conditional knockout mice results in an inhibition of tumor development that makes SIVA an interesting new candidate therapeutic target for the treatment of a carcinoma with few therapeutic options.

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Conflict of interest statement

Conflicts of interest:

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Context dependent outcome of SIVA expression. Left, E1A 12S expressing mouse embryo fibroblasts (MEFs) that are wild-type for p53 undergo apoptosis after DNA damage due to upregulation of Bbc3 (Puma), Pmaip1 (Noxa), Bax, and Siva, that are selectively expressed during apoptosis. Right, KRASG12D mutant NSCLC that also contains a wild-type p53 overexpresses SIVA. These cells proliferate and display a transformed phenotype. Upon SIVA knock-down, cells die by autophagy due to a pronounced reduction of mTOR activity.
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Comment on

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