“This means if people have a major wound, you can stimulate pathways to heal them faster,” says Steller. “But in a cancer patient you want to diminish those same pathways. It’s this slider between cancer and regeneration.”

But the dividing line may not be so clear-cut, he’s found. When a cell undergoes apoptosis, it also sends out signals to nearby cells encouraging them to divide, Steller has found. “The cell is saying ‘look, I’m going to die, you need to replace me,’” he explains. For wound healing, this means some level of apoptosis actually helps the process of healing. But in cancer, it introduces a problem: more apoptosis may increase the signals that tell nearby cells—including cancerous ones—to multiply.

This may mean that radiation therapy (which kills cancer through inducing widespread apoptosis) or one of Steller’s new small molecule compounds could force a cancer to spread at the same time it’s killing a primary tumor. If researchers like Steller can tease apart these growth-causing signals—called mitogens—from the rest of the apoptotic pathway, they’d be able to pick and chose which ones to turn on. For cancer, the ideal mix would be more apoptosis with no mitogens. For healing, the goal would be less apoptosis and a surplus of mitogens.

“Steller’s recent work,” says Horvitz, “is novel, important, and intriguing in the context of possible novel therapeutics.”

And whether or not his findings lead rapidly to therapeutics, his research is helping scientists understand how to control a cell’s most fundamental decisions: whether to live or die.

		Controlled Demolition Apoptosis doesn’t always kill a cell. In some cases, the process can stop midway, destroying some of a cell’s organelles or membranes, but not all. Sperm cells—which need to be light and speedy to fertilize an egg—carry only the most vital organelles. Steller has used his expertise in apoptosis to figure out this process, and it links back to cell suicide–blocking IAPs. These proteins surround the nucleus of a developing sperm cell, his lab team reported in the April 29, 2011, issue of Cell. So when apoptosis proceeds, the nucleus is protected. “This is a really exciting finding,” says Steller, “because it gives us a general model for how the cell death pathway is used for cellular remodeling, for controlled demolition.” Another instance of this type of targeted destruction is the remodeling of neurons, says Steller. When a neuron wants to change direction, it selectively destroys one branch in order to build another, using IAPs to control the breakdown. He hypothesizes that mistakes in how neurons control this apoptotic pathway may contribute to neurodegenerative diseases. –S.W.

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