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In breast cancer metastasis, researchers identify possible drug target

ancer stopped metastasis. But the researchers also found that if they knocked out the microRNA29b, tumors spread even in the presence of GATA3, suggesting that microRNA29b can be the driver of metastasis.

In the mouse models of breast cancer studied by Werb's team, GATA3 normally restrains cancerous cells from breaking away from the main tumor and migrating to other organs.

It might be possible, Werb said, to develop drugs that inhibit breast cancer metastasis by re-activating these controls in cancerous cells that have lost the normal protein.

Many researchers who study early stages of cancer focus on abnormal genes and proteins that cause cells to expand their numbers rapidly, a hallmark of cancer.

However, the ability to spread to distant places and to eventually cause lethal complications requires not only cell division and tumor growth, but also changes in how the cancerous cell negotiates with its surroundings. This relationship must be altered to permit cancer to spread, according to earlier research findings by Werb and others.

"Many of the key processes in cancer that GATA3 suppresses take place outside the cell, in the surrounding environment," she said.

GATA3 is a master control for luminal cells, which line the milk-carrying ducts of the breast. In essence, GATA3 dictates the defining characteristics of a normal breast cell, Werb said.

Luminal breast cancers are the most common form of the disease, and the hormones estrogen and progesterone drive their growth. Loss of the normal GATA3 protein as luminal breast cancers evolve is associated with a greater risk of death, Werb said, and occurs in roughly 10 percent of luminal breast cancer cases.

But, along with many other proteins, GATA3 also is absent in "triple negative," breast cancers, which are more often fatal. Triple negative breast cancers, which disproportionately affect black women and younger women, do not depend on the horm

Contact: Jeffrey Norris
University of California - San Francisco

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