( Everyone has moles. Most of the time t...)Why don't all moles progress to melanoma?

Everyone has moles. Most of the time, they are nothing but a cosmetic nuisance. But sometimes pigment-producing cells in moles called melanocytes start dividing abnormally to form a deadly form of skin cancer called melanoma. About one in 65 Americans born this year will be diagnosed with melanoma at some point during their lifetime.

Scientists know that 30 percent of all melanomas begin in a mole. They know that 90 percent of moles contain cancer-causing mutations. What scientists didn't know is how melanocytes stop these mutations from triggering the development of cancer.

Maria S. Soengas, Ph.D., and other scientists in the Multidisciplinary Melanoma Clinic at the University of Michigan Comprehensive Cancer Center, have found the answer to this important question in an unexpected place ?a structure inside cells called the endoplasmic reticulum, or ER.

"Our results support the direct role of the endoplasmic reticulum as an important gatekeeper of tumor control," says Soengas, who is an assistant professor of dermatology in the U-M Medical School. "Until now, no one knew there was a connection between ER stress and the very early stages of tumor initiation."

Results of the U-M study ?involving melanocytes from normal human skin and biopsies of non-malignant human moles ?are being published in the October issue of Nature Cell Biology.

The endoplasmic reticulum is the cell's protein production factory. The process begins when chains of amino acids are deposited in the ER membrane in response to coded instructions from genes. Chaperone proteins fold these amino acids into specific shapes. When too many of them build up in the membrane, or when something goes wrong with the folding process, the system gets bogged down. This can stress or even kill the cell.

To prevent this, the ER sends out distress signals to activate what scientists call the unfolded protein response (UPR). This slows the protein production proc
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Source:University of Michigan Health System

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