Intervallic cell

Atonality isn’t exactly setting the world on fire these days, what with all these whippersnappers and their feel-good postminimalism. Maybe it needs a new marketing hook. Hmmm… how about “possible cure for cancer”?

Our genetic evidence from Drosophila and previous in vitro studies of mammalian Atonal homolog 1 (Atoh1, also called Math1 or Hath1) suggest an anti-oncogenic function for the Atonal group of proneural basic helix-loop-helix transcription factors. We asked whether mouse Atoh1 and human ATOH1 act as tumor suppressor genes in vivo. Genetic knockouts in mouse and molecular analyses in the mouse and in human cancer cell lines support a tumor suppressor function for ATOH1.

From W. Bossuyt et al., Atonal homolog 1 Is a Tumor Suppressor Gene,” published February 24 in the journal PLoS Biology. OK, they’re not talking about music. What are they talking about?

The atonal gene was first isolated in fruit flies in 1993 by a team led by Andrew P. Jarman. It’s a proneural gene, which means it activates some part of the embryonic development of the nervous system—in this case, chordotonal organs, cell structures designed to pick up vibrations (think eardrums and the like). The name comes from the fact that an atonal mutation will disrupt the development of chordotonal organs.

As it turns out, a very similar gene, Atonal homolog 1, controls the development secretory cells in the lining of the colon in both humans and mice—and, as Bossyut and his team discovered, inactivating Atoh1 in mice triggers the onset of colon cancer. What’s more, the majority of human cases of colon cancer the team studied were found to correspond with an inactive ATOH1 gene as well.

The obvious implication of the results is that an ATOH1 screening could provide an early-warning system for colon cancers. But more interestingly, atonal genes can be chemically reactivated:

[T]reatment of [colon cancer] patients whose tumors show epigenetic silencing of ATOH1 with DNA methyltransferase inhibitors might prove a powerful avenue for therapy, because it appears to be sufficient to restore ATOH1 expression and induce cancer cell death.

That’s the most dissonant good news I’ve heard all day.

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