Journal
JOURNAL OF CELL SCIENCE
Volume 134, Issue 11, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.258316
Keywords
p53; Amyloid; Prion; Tumor suppressor; Tumorigenesis; Cancer initiation
Categories
Funding
- Department of Science and Technology, Ministry of Science and Technology, India [EMR/2014/001233, CRG/2019/001133]
- University Grants Commission-Council of Scientific & Industrial Research (UGC-CSIR), Government of India
- Department of Science and Technology Science and Engineering Research Board, Government of India
Ask authors/readers for more resources
The formation of wild-type p53 amyloid was found to confer oncogenic properties to non-cancerous cells, promoting enhanced survival, apoptotic resistance, increased proliferation, and migration through cell generations. Tumorigenic potential of p53 amyloid-transformed cells was further confirmed in mouse xenografts, where p53 amyloids were present.
Tumor suppressor p53 mutations are associated with more than 50% of cancers. Aggregation and amyloid formation of p53 is also implicated in cancer pathogenesis, but direct evidence for aggregated p53 amyloids acting as an oncogene is lacking. Here, we condusively demonstrate that wild-type p53 amyloid formation imparts oncogenic properties to non-cancerous cells. p53 amyloid aggregates were transferred through cell generations, contributing to enhanced survival, apoptotic resistance with increased proliferation and migration. The tumorigenic potential of p53 amyloid-transformed cells was further confirmed in mouse xenografts, wherein the tumors showed p53 amyloids. p53 disaggregation rescued the cellular transformation and inhibited tumor development in mice. We propose that wild-type p53 amyloid formation contributes to tumorigenesis and can be a potential target for therapeutic intervention. This article has an associated First Person interview with the first author of the paper.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available