Protein May Stop Melanoma Before It Starts
A single protein may enable skin cells to detect genetic damage and stop growing rather than become cancerous, researchers are reporting.
The protein, IGFBP7, regulates an anticancer mechanism in normal cells that allows the cells to enter a state of arrested growth or commit suicide rather than develop into melanomas in the face of genetic damage. Understanding this process could lead to new strategies for treating the disease, the researchers say.
Dr. Michael Green of the University of Massachusetts Medical School and his colleagues reported their findings in the February 8 Cell.
The anticancer response of normal cells is thought to be important in preventing cancer, but sometimes it fails. To understand why, Dr. Green's group conducted a genome-wide screen for genes involved in preventing melanoma in cells with cancer-causing mutations in the BRAF gene.
The search yielded 17 genes, including some well-known tumor suppressors such as p53.
Further experiments indicated that IGFBP7 was both necessary and sufficient to arrest growth. The protein is part of a negative-feedback loop that disrupts the growth-promoting signals of the protein produced by the BRAF gene.
The researchers note that the activity of IGFBP7 increases in moles with BRAF mutations but not in melanoma cells with the same mutations. This could explain why most moles do not progress to cancer despite the genetic flaws.
"When IGFBP7 is expressed, a mole remains a mole," says Dr. Green. But in melanoma cells, the protein is lost and the anticancer response fails.
Experiments in mice showed that IGFBP7 has a potent antitumor effect on human tumors derived from BRAF-mutated melanoma cells. But the protein may have little or no effect on tumors containing normal BRAF genes.
Whether the stunning antitumor effects will be seen in humans remains to be seen. But the findings demonstrate the promise of inducing a state of arrested growth, or senescence, as a therapeutic strategy for cancer, notes an accompanying editorial.
"Undoubtedly, mutations that activate or repress cellular senescence will be crucial in the progression of many other human malignancies," write Drs. Yuchen Chien and Scott W. Lowe of the Cold Spring Harbor Laboratory.
—Edward R. Winstead