Mutants of p53 sustain tumor growth under mechanical compression
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Context
Solid tumors are subjected to mechanical stimuli arising from their growth in confined environments. Growth-induced pressure builds up in tumors such as pancreatic cancer and rises alongside the occurrence of genetic alterations during tumorigenesis. This study aims to understand the so far unknown relationship between genetic alterations and cancer cell behavior under compressive stress.
Results
Using isogenic cell lines with engineered p53 mutations, we showed that the p53 background influences cell response to compression. Tumor growth under compression increased in cells harboring a mutated-truncated p53 form. This mutation blocked caspase 3 cleavage and promoted survival and growth through PI3K-AKT activation and dysregulation of c-FOS and FOSB transcription factors network. Mutated-truncated p53 cells displayed a unique behavior and heightened an activation state under compression.
Conclusion
Mechanical compression and p53 mutations together drive tumor growth. p53 status could be a biomarker for predicting tumor adaptation to mechanical stress and efficiency of therapies targeting mechanosensitive pathways.
Teaser
Mechanical compression and p53 mutations together enhance cancer cell survival and growth, driving solid tumor progression.
