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Updated: Jul 10, 2026
SA-β-Galactosidase-Based Screening Assay for the Identification of Senotherapeutic Drugs
Published on: June 28, 2019
Cellular senescence bypass screen identifies new putative tumor suppressor genes
J F M Leal1, J Fominaya, A Cascón
1Experimental Therapeutics Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
We identified five genes that bypass senescence when their function is lost, suggesting they regulate cell lifespan and tumor suppression. Three of these genes (Csn2, Aldose reductase, Brf1) show reduced expression or genomic loss in human tumors.
Area of Science:
- Cell Biology
- Genetics
- Oncology
Background:
- Cellular senescence limits lifespan and prevents uncontrolled proliferation, acting as a tumor suppressor mechanism.
- Identifying genes that regulate senescence is crucial for understanding tumorigenesis.
Purpose of the Study:
- To discover novel senescence regulatory genes involved in tumor suppression.
- To investigate the role of identified genes in human cancers.
Main Methods:
- A large-scale antisense-based genetic screen was performed in primary mouse embryo fibroblasts (MEFs).
- Gene expression and genomic losses were analyzed in human tumors using Northern blot and quantitative reverse transcriptase-PCR.
Main Results:
- Five genes (csn2, aldose reductase, brf1, S-adenosyl homocysteine hydrolase, Bub1) were identified, whose loss-of-function partially bypasses senescence.
- Inactivation of these genes conferred resistance to p53- and p16INK4a-induced proliferation arrest.
- Expression loss and genomic losses (including heterozygous deletions) of Csn2, Aldose reductase, and Brf1 were observed in various human tumors.
Conclusions:
- Csn2, Aldose reductase, and Brf1 function as putative tumor suppressors.
- These genes are located at chromosomal regions frequently altered in cancer (15q21.2, 7q35, and 14q32.33).
- The identified genes represent novel regulators of senescence and potential targets for cancer therapy.
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