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<p>Several bat species live &gt;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 <i>Myotis lucifugus</i>, <i>Eptesicus fuscus</i>, <i>Eonycteris spelaea</i>, and <i>Artibeus jamaicensis</i> – 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 <i>TP53</i> and <i>MDM2</i> transcripts and elevated p53-dependent apoptosis. <i>M. lucifugus</i> shows a genomic duplication of <i>TP53</i>. 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.</p>

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Limited cell-autonomous anticancer mechanisms in long-lived bats

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月3日

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  • Fathima Athar,
  • Zhizhong Zheng,
  • Sebastien Riquier,
  • Max Zacher,
  • J. Yuyang Lu,
  • Yang Zhao,
  • Valentin Volobaev,
  • Dominic Alcock,
  • Alex Galazyuk,
  • Lisa Noelle Cooper,
  • Tony Schountz,
  • Lin-Fa Wang,
  • Emma C. Teeling,
  • Andrei Seluanov,
  • Vera Gorbunova

摘要

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.