So far, only dogs, Tasmanian devils, and four bivalve species are known to carry transmissible cancers, which have varying effects on their hosts.
Host species | Domestic dog (Canis lupus familiaris) | Tasmanian devil (Sarcophilus harrisii) | Bivalves (the soft-shelled clam, Mya arenaria, the mussel, Mytilus trossulus, and the cockle species, Cerastoderma edule, and the golden carpet-shell clam, Poltitapes aureus) |
Cancer | Canine transmissible venereal tumor (CTVT) | Devil’s facial tumor disease (DFT1 and DFT2) | Clam disseminated neoplasia |
Outcome | GABRIELE MARINO, UNIVERSITY OF MESSINA, ITALY | CAMILA ESPEJO, UNIVERSITY OF TASMANI |
In one of the most extensive studies of devil facial tumor disease (DFT1) to date, an international team of researchers has uncovered a mechanism that drives the cancer’s metastasis and helps it to evade the Tasmanian devils’ immune system.
1 | Cancer cells that form DFT1 tumors overproduce transmembrane enzymes known as ERBB receptors. |
2 | When stimulated by specific proteins—likely EGF and NRG1, which are also overproduced in DFT1 cells—ERBB receptors induce production of a signaling protein and transcription factor called Stat3 and drive its activation. |
3 | In the nucleus, Stat3 drives the production of genes such as MMP2 that are known to trigger metastasis in humans. |
4 | Stat3 also binds to and inhibits another transcription factor, Stat1, which normally drives the expression of genes necessary for the generation of MHC class I molecules. |
5 | MHC class I molecules normally interact with receptors on cytotoxic T cells to discriminate self from foreign cells. By downregulating the production of MHC proteins, DFT1 cells are able to evade detection by the animals’ immune system. |
6 | Under normal circumstances, cells lacking MHC markers would be detected by natural killer cells (NK), but for reasons that are unclear, devil NK cells don’t react to DFT1. |
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