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The Mysteries of TGF-Beta

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In breast cancer, the TGF-beta signaling pathway can act as both a tumor suppressor and a tumor promoter, and a new study in the journal Oncogene details how and when, reports Garth Sundem at Science2.0. "Basically, a tumor hijacks an embryonic program and turns it back on," senior author Heide Ford tells Sundem. As embryos grow, they rely on a transcription factor called SIX1 to proliferate their cells quickly, and turn off SIX1 as adults. But the new study shows that some breast cancers turn SIX1 back on, turning TGF-beta from a tumor suppressor to a tumor promoter, Sundem says. "In this case, SIX1's microRNAs attach to and mute the section of TGF-beta that stops cell growth," he adds. "With TGF-beta silenced, the signal does nothing to stop cell growth, and instead encourages these cells to migrate into new tissues. Turning on SIX1 and its associated microRNAs is like removing the speed governor from a reckless teenager's Mustang convertible."

Ford says this means a high level of SIX1 expression is a signal that a breast tumor is using TGF-beta to proliferate, and those patients could then take TGF-beta inhibitors as part of their treatment.

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