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Cited by 784

The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.

High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat

Open access
Tian, Xiao, Azpurua, Jorge, Hine, Christopher, Vaidya, Amita, Myakishev-Rempel, Max, Ablaeva, Julia, Mao, Zhiyong, Nevo, Eviatar, Gorbunova, Vera, Seluanov, Andrei·2013·Nature
DOI 10.1038/nature12234
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Abstract

The naked mole rat (Heterocephalus glaber) displays exceptional longevity, with a maximum lifespan exceeding 30 years. This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4 years. In addition to their longevity, naked mole rats show an unusual resistance to cancer. Multi-year observations of large naked mole-rat colonies did not detect a single incidence of cancer. Here we identify a mechanism responsible for the naked mole rat’s cancer resistance. We found that naked mole-rat fibroblasts secrete extremely high-molecular-mass hyaluronan (HA), which is over five times larger than human or mouse HA. This high-molecular-mass HA accumulates abundantly in naked mole-rat tissues owing to the decreased activity of HA-degrading enzymes and a unique sequence of hyaluronan synthase 2 (HAS2). Furthermore, the naked mole-rat cells are more sensitive to HA signalling, as they have a higher affinity to HA compared with mouse or human cells. Perturbation of the signalling pathways sufficient for malignant transformation of mouse fibroblasts fails to transform naked mole-rat cells. However, once high-molecular-mass HA is removed by either knocking down HAS2 or overexpressing the HA-degrading enzyme, HYAL2, naked mole-rat cells become susceptible to malignant transformation and readily form tumours in mice. We speculate that naked mole rats have evolved a higher concentration of HA in the skin to provide skin elasticity needed for life in underground tunnels. This trait may have then been co-opted to provide cancer resistance and longevity to this species.

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Metadata

Authors
Tian, X., Azpurua, J., Hine, C., Vaidya, A., Myakishev-Rempel, M., Ablaeva, J., Mao, Z., Nevo, E., Gorbunova, V., & Seluanov, A.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2013-06-19
Volume
499
Issue
7458
Pages
346-349
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature12234
OpenAlex
W1983883185
Cited by
784
References
4
FWCI
32.45
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. https://app.cochat.ai/papers/10.1038/nature12234
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Tian, X., Azpurua, J., Hine, C., Vaidya, A., Myakishev-Rempel, M., Ablaeva, J., Mao, Z., Nevo, E., Gorbunova, V., & Seluanov, A. (2013). High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature. https://doi.org/10.1038/nature12234

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.