Researchers at the Moffitt Cancer Center recently published a study entitled “β-arrestin-1 mediates nicotine-induced metastasis through E2F1 target genes that modulate epithelial-mesenchymal transition”, where they identify two important proteins responsible for nicotine-induced metastasis in lung cancer. The study was published in the journal Cancer Research.
Lung cancer is the lead cause of cancer deaths both in the U.S. and worldwide. An estimated 159,000 lung cancer deaths were reported last year in the United States, with cigarette smoking accounting as the main risk factor for the development of this malignancy.
Nicotine present in cigarettes is a highly addictive compound, capable of stimulating proliferation and invasion of cancer cells and blocking cell death, two well-known features of aggressive cancers. Nicotine is also able to induce cancerous cells to alter their shape, increase motility and turn metastatic, meaning that they can spread to other parts and organs of the body. In fact, the majority of lung cancer deaths are associated with the dissemination of cancer to other organs.
The research team found that nicotine can stimulate the protein beta-arrestin-1, which in turn promotes the production of specific proteins by cancer cells that have increased motility and invasion power, resulting in the spread of metastatic lung cancer cells.
The team found that beta-arrestin-1 protein associates in the nucleus with another protein – E2F1 – causing the development of metastatic cells. E2F1 was previously found to promote cancer cell proliferation, however, this is the first report demonstrating this protein also contributes to lung cancer metastasis.
These findings were observed both in mice and human lung cancer cells. The researchers found that samples with high levels of beta-arrestin-1 also had high levels of proteins known to be related to cell adhesion and motility. Interestingly, in animal models, it was possible to halt the growth and metastasis of lung cancer cells by blocking beta-arrestin-1, suggesting that targeting this protein could be a potential therapeutic strategy for preventing metastatic disease.
Study’s leading author, Dr. Srikumar Chellappan stated in a news release, “we expect that this study will lead to new therapeutic strategies to combat cancer metastasis. For example, inhibiting the binding of beta-arrestin-1 to E2F1 would be a potential avenue to prevent metastasis. Identification and development of novel drugs that can target beta-arrestin-1 can be an important step in this direction.”