Publication Date:
2013-06-21
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3720720/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3720720/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tian, Xiao -- Azpurua, Jorge -- Hine, Christopher -- Vaidya, Amita -- Myakishev-Rempel, Max -- Ablaeva, Julia -- Mao, Zhiyong -- Nevo, Eviatar -- Gorbunova, Vera -- Seluanov, Andrei -- R01 AG027237/AG/NIA NIH HHS/ -- R01 AG031227/AG/NIA NIH HHS/ -- England -- Nature. 2013 Jul 18;499(7458):346-9. doi: 10.1038/nature12234. Epub 2013 Jun 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of Rochester, Rochester, New York 14627, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23783513" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Sequence
;
Animals
;
Cell Proliferation
;
Cell Transformation, Neoplastic/*metabolism
;
Cells, Cultured
;
Contact Inhibition
;
Disease Resistance
;
Fibroblasts/metabolism
;
Glucuronosyltransferase/chemistry
;
Guinea Pigs
;
Humans
;
Hyaluronic Acid/*metabolism
;
Mice
;
Mole Rats
;
Molecular Sequence Data
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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