Fly Eyes Run Amok
What can Drosophila eyes tell us about the origins of cancer?
William Aryitey |
A transcription factor found in fruit fly eyes may offer insight into human oncogenesis, according to a new study (1). Yan is an ETS-domain transcription factor that helps regulate cell differentiation in fruit flies. When cells specialize, the levels of Yan expression fluctuate, which is known as ‘noise’.
This noise peaks as cells differentiate, causing fluctuations in Yan expression even between neighboring cells. Richard Carthew, principle investigator and Program Director at the Robert Lurie Cancer Center in Chicago, expands: “It is surprising because usually cells within a tissue make very similar amounts of the molecules important for their livelihood – which ensures a cooperative and homogeneous ‘society’ of cells. Instead, we saw a brief period of what looked like molecular anarchy.”
“It reminds me of that great Star Trek episode in which Spock, like all Vulcans, goes through a brief but crazed ‘Amok Time’. Before and after, all is peaceful, harmonious and logical with Vulcans. We think Yan also has an amok time that is needed for stem cells to transition into a specialized state.”
Carthew has an intriguing theory on how this could relate to the oncogene TEL-1; Yan’s human homolog. He suggests that, perhaps cancer cells somehow move back to this “amok time” and are stuck there. “It would explain the heterogeneity of tumor cells and why they are not responsive to signals the body provides to put them under control. Another oncogene called EGFR (or HER2) is required for cells to leave amok time and go back to normal. If this signal breaks down – as it might in cancer – they could permanently go back to this state of instability,” says Carthew.
The research team plans to continue their investigation of Yan, looking to see how common the noisy transition is for other cell types. Carthew says, “Other molecules besides Yan could run amok and we are tagging them to see if similar things happen. We also want to know in detail how this comes about and how it can be turned off. Knowing these important details might provide clues about how to design therapies that turn down the noise within cancer patients.”
- N Pelaez et al., “Dynamics and heterogeneity of afate determinant during transition towards cell differentiation”, eLife 19, 4, pii: e08924 (2015).