Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2023 Jan 10;120(2):e2219963120.
doi: 10.1073/pnas.2219963120. Epub 2023 Jan 4.

WRN suppresses p53/PUMA-induced apoptosis in colorectal cancer with microsatellite instability/mismatch repair deficiency

Robert W Sobol  1   2
Affiliations
Comment

WRN suppresses p53/PUMA-induced apoptosis in colorectal cancer with microsatellite instability/mismatch repair deficiency

Robert W Sobol. Proc Natl Acad Sci U S A. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

The author declares no competing interest.

Figures

Fig. 1.
Fig. 1.
Loss of WRN expression via RNA interference or gene KO, as well as inhibition of WRN’s helicase activity, triggers an increase in DNA damage accompanied by ATM and CHK2 activation. This initiates the induction of p53 expression and activation followed by TIP60-mediated p53 acetylation that triggers induction of PUMA and Bax, while DNA damage can also directly lead to PUMA induction. Once activated, PUMA selectively triggers the onset of mitochondrial-mediated apoptosis in colorectal cancer cells/tumors with microsatellite instability/mismatch repair deficiency. The onset of WRN inhibition (WRNi) induced apoptosis is demonstrated in cell lines, tumor models, and patient-derived xenograft (PDX) tumors.
See this image and copyright information in PMC

Comment on

References

    1. Cronin K. A., et al. , Annual report to the nation on the status of cancer, part 1: National cancer statistics. Cancer 128, 4251–4284 (2022). - PMC - PubMed
    1. Hampel H., Kalady M. F., Pearlman R., Stanich P. P., Hereditary colorectal cancer. Hematol. Oncol. Clin. North Am. 36, 429–447 (2022). - PubMed
    1. Idos G., Valle L., "Lynch syndrome" in GeneReviews((R)), Adam M. P., et al., Eds. (University of Washington, Seattle (WA), 1993).
    1. Hao S., et al. , Synthetical lethality of werner helicase and mismatch repair deficiency is mediated by p53 and PUMA in colon cancer. Proc. Natl. Acad. Sci. U.S.A. 119, e2211775119 (2022). - PMC - PubMed
    1. Srivas R., et al. , A network of conserved synthetic lethal interactions for exploration of precision cancer therapy. Mol. Cell 63, 514–525 (2016). - PMC - PubMed

Publication types

Substances

Supplementary concepts