Limited cell-autonomous anticancer mechanisms in long-lived bats
Abstract Several bat species live >20–40 years, suggesting that they possess efficient anti-aging and anti-cancer defenses. Here we investigate the requirements for malignant transformation in primary fibroblasts from four bat species Myotis lucifugus, Eptesicus fuscus, Eonycteris spelaea, and Ar...
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| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59403-z |
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| Summary: | Abstract Several bat species live >20–40 years, suggesting that they possess efficient anti-aging and anti-cancer defenses. Here we investigate the requirements for malignant transformation in primary fibroblasts from four bat species Myotis lucifugus, Eptesicus fuscus, Eonycteris spelaea, and Artibeus jamaicensis – spanning the bat evolutionary tree and including the longest-lived genera. We show that bat fibroblasts do not undergo replicative senescence, express active telomerase, and show attenuated SIPs with dampened secretory phenotype. Unexpectedly, unlike other long-lived mammals, bat fibroblasts are readily transformed by two oncogenic “hits”: inactivation of p53 or pRb and activation of HRASG12V. Bat fibroblasts exhibit increased TP53 and MDM2 transcripts and elevated p53-dependent apoptosis. M. lucifugus shows a genomic duplication of TP53. We hypothesize that some bat species have evolved enhanced p53 activity as an additional anti-cancer strategy, similar to elephants. Further, the absence of unique cell-autonomous tumor suppressive mechanisms may suggest that in vivo bats may rely on enhanced immunosurveillance. |
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| ISSN: | 2041-1723 |