Limited cell-autonomous anticancer mechanisms in long-lived bats
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 HRAS<sup>G12V</sup>. 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.
Authors
- Emma C. Teeling (ORCID: https://orcid.org/0000-0002-3309-1346)
- Tony Schountz (ORCID: https://orcid.org/0000-0002-1292-7650)
- Valentin P. Volobaev (ORCID: https://orcid.org/0000-0001-7355-9882)
- Max Zacher (ORCID: https://orcid.org/0000-0003-0377-7221)
- Lin‐Fa Wang (ORCID: https://orcid.org/0000-0003-2752-0535)
- Sébastien Riquier (ORCID: https://orcid.org/0000-0002-4207-2470)
- Vera Gorbunova (ORCID: https://orcid.org/0000-0001-8979-0333)
- Dominic Alcock (ORCID: https://orcid.org/0000-0001-8942-2362)
- Lisa Noelle Cooper (ORCID: https://orcid.org/0000-0002-1765-927X)
- Andrei Seluanov (ORCID: https://orcid.org/0000-0003-3400-538X)
- Alexander V. Galazyuk (ORCID: https://orcid.org/0000-0003-2765-9430)
- Fathima Athar (ORCID: https://orcid.org/0000-0002-0608-6162)
- Zhizhong Zheng (ORCID: https://orcid.org/0000-0003-0352-4806)
- Yang Zhao (ORCID: https://orcid.org/0000-0002-8703-3678)
- Jinlong Y. Lu (ORCID: https://orcid.org/0000-0003-3170-5655)
Institutions
- University College Dublin (IE)
- SingHealth (SG)
- University of Rochester Medical Center (US)
- SingHealth Duke-NUS Academic Medical Centre (SG)
- Duke-NUS Medical School (SG)
- University of Rochester (US)
- Colorado State University (US)
- Northeast Ohio Medical University (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-05-03
- DOI
- https://doi.org/10.1038/s41467-025-59403-z
- Citations
- 16
- Primary Topic
- Bat Biology and Ecology Studies
- Type
- article
- Field-Weighted Citation Impact
- 48.43
Funders
- University of Rochester
- Duke-NUS Medical School
- National Research Foundation
- National Research Foundation Singapore
- National Institutes of Health
- Medical Research Council
- National Medical Research Council
- Office of Extramural Research, National Institutes of Health