The Cancer Gene You Knew Was Doing a Second Job You Didn't

Most people who have heard of BRCA1 know one thing about it: it is the cancer gene. The one tied to hereditary breast and ovarian cancer, the one behind the conversations about testing and preventive surgery, the one Angelina Jolie turned into a household name. The story attached to it is a story about repair. Your DNA takes damage constantly, and BRCA1 helps mend the breaks. When the gene is lost, the breaks pile up, the cell's instructions get garbled, and cells go rogue. That story is true. It just turns out to be only half of one.

Because what kills most women with ovarian cancer is not the first tumor. It is where the cancer goes next. The lethal event is the spread, when cells break loose from the original site and seed themselves in distant organs. And cancers missing BRCA1 are unusually good travelers. The repair story explains why these tumors form. It has never really explained why they move.

A new study finds that BRCA1 was holding down a second job. When the gene is working, it keeps a particular cellular pump switched off, a pump whose only purpose is to pull a nutrient called choline into the cell. Choline is nothing exotic; it is in eggs, liver, soybeans. But when BRCA1 is gone, the pump runs wide open, and choline pours in. The cell converts it into a related compound — and that compound is a message, not a spent byproduct or a bit of metabolic ash. It latches directly onto a protein inside the cell and props it up, and that protein's job is to tell the cell to loosen its grip on its neighbors, change its shape, and start crawling. The cell's chemistry, in other words, is issuing orders. The choline pipeline is the command to invade.

The researchers built the case from several directions. They mapped the chemical differences between healthy cells and BRCA1-deficient ones. They tagged choline so they could watch it flow through the system. And they jammed the pump, both by switching it off genetically and by treating cells with an experimental drug, in lab dishes and in mice. Each time, cutting off the fuel cut off the message, and the urge to spread stopped.

That drug is early, and the road from a mouse to a person is long and littered with failures; this paper does not pretend to walk it. What it does is rearrange how we file a famous gene. BRCA1 lived under the heading "DNA repair." It apparently also belongs under something like "metabolic policing," watching what the cell eats and what that food is allowed to say. The cell does not sort itself into our tidy categories. When one gene fails, it can swing open more than one door at once. That is the part worth keeping, not as a cure on the horizon, but as a correction to how completely we thought we understood the thing.