In a new study published in the Journal of Cell Biology, scientists show how a protein common in human cells appears to switch on metastasis in cancer cells. They suggest the discovery will help us better understand epithelial cancers like breast and lung cancer.
In childhood, our bodies are still growing, and it is normal for our cells to migrate. But as we stop growing, it is much less common for cells to travel.
Cancer cells, however, have a much greater ability to migrate than normal cells in adulthood. This is how cancer establishes new, secondary tumors in other parts of the body – a process known as metastasis, which is responsible for 90% of cancer deaths.
For the new study, a team from McGill University in Montreal, Canada focused on a protein called DENND2B, which appears to play an active role in the normal migration of cells.
Lead investigator Peter McPherson, a James McGill Professor who leads a lab at McGill’s Montreal Neurological Institute, explains what they found:
“DENND2B activates another protein in the cell called Rab13, which is an enzyme that promotes cell migration. Until now, we didn’t know how Rab13 was activated to initiate cell migration.”
The team discovered that in many types of cancer – especially epithelial cancers that often metastasize to the brain – Rab13 is unusually highly expressed.
Epithelial tissue comprises closely packed layers of cells to form the covering or lining of internal and external body surfaces. Skin is an example of epithelial tissue, as is the lining of body cavities like the chest cavity and the abdominal cavity. Epithelial tissue also lines surfaces in and around organs such as the breast and the lung.
Epithelial cancers – known as carcinomas – arise in cells of epithelial tissue and account for the vast majority of cancers, including breast, prostate, lung, colon, ovarian and bladder cancer. They are distinct from other cancers such as cancers of the blood and lymphatic system (known as leukemias and lymphomas), and cancers that arise in connective tissue (known as sarcomas).
In their study, the researchers found that DENND2B activates Rab13 at the leading edge of the cancer cell, and this appears to be an important point for cell migration. They note:
“DENND2B interacts with the Rab13 effector MICAL-L2 at the cell periphery, and this interaction is required for the dynamic remodeling of the cell’s leading edge.”
In another part of the study, the researchers injected very aggressive human cancer cells in two groups of mice. One group of mice had cells with high levels of Rab13 protein and the other group of mice was genetically engineered to lack the Rab13 gene, so they had none of the protein.
When they examined the results, Prof. McPherson says they found:
“In the case of the cells with reduced Rab13 levels, the cancer either did not grow at all or formed a smaller tumor. Furthermore, the smaller tumor did not metastasize into other tissue.”
He notes that theirs is the first study to consider experimenting with Rab13 in relation to cancer.
The team believes the study will generate great interest in using Rab13 as a target in cancer therapies, but cautions there is still a long way to go before we start seeing it in clinical trials.
Funds from the Canadian Institutes of Health Research and the National Institutes of Health helped finance the study.
Meanwhile, Medical News Today recently reported how another team from the University of Manchester in the UK has discovered that the nanomaterial graphene can target and neutralize cancer stem cells. Cancer stem cells are thought to be important drivers of tumor recurrence and metastasis. Reporting in the journal Oncotarget, the scientists suggest graphene may have potential to treat a range of cancers with fewer side-effects than many current therapies.