Deficiency in mammalian STN1 promotes colon cancer development via inhibiting DNA repair

Despite the high lethality of colorectal cancers (CRCs), only a limited number of genetic risk factors are identified. The mammalian ssDNA-binding protein complex CTC1-STN1-TEN1 protects genome stability, yet its role in tumorigenesis is unknown. Here, we show that attenuated CTC1/STN1 expression is...

Full description

Saved in:
Bibliographic Details
Published in:Science advances 2023-05, Vol.9 (19), p.eadd8023-eadd8023
Main Authors: Nguyen, Dinh Duc, Kim, Eugene, Le, Nhat Thong, Ding, Xianzhong, Jaiswal, Rishi Kumar, Kostlan, Raymond Joseph, Nguyen, Thi Ngoc Thanh, Shiva, Olga, Le, Minh Thong, Chai, Weihang
Format: Article
Language:English
Subjects:
Animals
Biomedicine and Life Sciences
Cancer
Colonic Neoplasms - genetics
DNA Repair
DNA Replication
Mammals - genetics
Mice
SciAdv r-articles
Telomere - metabolism
Telomere-Binding Proteins - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Despite the high lethality of colorectal cancers (CRCs), only a limited number of genetic risk factors are identified. The mammalian ssDNA-binding protein complex CTC1-STN1-TEN1 protects genome stability, yet its role in tumorigenesis is unknown. Here, we show that attenuated CTC1/STN1 expression is common in CRCs. We generated an inducible STN1 knockout mouse model and found that STN1 deficiency in young adult mice increased CRC incidence, tumor size, and tumor load. CRC tumors exhibited enhanced proliferation, reduced apoptosis, and elevated DNA damage and replication stress. We found that STN1 deficiency down-regulated multiple DNA glycosylases, resulting in defective base excision repair (BER) and accumulation of oxidative damage. Collectively, this study identifies STN1 deficiency as a risk factor for CRC and implicates the previously unknown STN1-BER axis in protecting colon tissues from oxidative damage, therefore providing insights into the CRC tumor-suppressing mechanism.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.add8023