The work, which appears in the March 18 issue of Science, is the first published research implicating the protein, collagen VII, in cancer.
The finding came about because roughly two-thirds of children with a blistering skin disorder called recessive dystrophic epidermolysis bullosa, or RDEB - caused by a mutation that leads to an altered or missing collagen VII protein - develop a type of skin cancer called squamous cell carcinoma. This led Paul Khavari, MD, PhD, the Carl J. Herzog Professor in Dermatology, to suspect that the protein had something to do with cancer formation.
What Khavari and postdoctoral scholar Susana Ortiz-Urda, MD, PhD, found is that a fragment of collagen VII is required for the skin cancer cells to break free from the neighboring skin tissue and spread - a step that turns an otherwise benign tumor into a killer. "When we blocked this sequence we also blocked the cancer from spreading," said Khavari, who is also chief of dermatology at the Veterans Affairs Palo Alto Health Care System.
The group found this sequence by studying skin samples from 12 children with RDEB. They used laboratory tools to activate molecular switches that normally turn skin cells cancerous. What they found was surprising. Four of the 12 samples never turned cancerous, no matter what cancer-promoting molecular switches the researchers had flicked. The remaining eight samples became cancerous much like normal skin cells that the researchers had studied previously.