An interaction between the integrin beta-1 (β1) and the cell surface signalling protein c-Met has been determined to aid survival of cells that have broken away from a primary tumor in a study from researchers at Barts Cancer Institute (London, UK).
Cells that break away from the primary tumor and thus the relative protection of attachment to other cells and the tumor microenvironment become more vulnerable to cell death. Determining how these cells are able to survive and therefore spread around the body and seed secondary tumors is a key task for cancer researchers.
“Metastasis is currently incurable and remains one of the key targets of cancer research. Our research advances the knowledge of how two key molecules communicate and work together to help cancer cells survive during metastasis. We’re hoping that this might lead to the discovery of new drugs to block the spread of cancer within the body,” commented study lead Stéphanie Kermorgant of Barts Cancer Institute.
This investigation, published recently in Nature Communications, involved examination of the changes that occur in cancer cells as they break away from tumors in cell cultures, zebrafish and mice. Through these investigations, the Barts team determined that when cancer cells are ‘floating’ free from the primary tumor, integrins diverge from their adhesion role and begin a novel form of intracellular signalling that the researchers termed ‘inside-in’ signalling.
Specifically, β1 and the cell surface signalling protein c-Met pair together and move inside the cell, where they target an area ordinarily associated with degradation and recycling of cellular material. This location is then harnessed for cell communication, with the two proteins signalling the rest of the cell to resist death while floating during metastasis.
Investigating their findings in both breast and lung cancer cells, it was determined that metastases were less likely to form when β1 and c-Met were blocked from entering the cell together or were prevented from travelling within the cell.
Integrins already represent a major target within cancer drug development, although agents that target their adhesive function have had limited success. The Barts team hope that these insights may lead to the design of better therapies against metastasis and more effective treatment combinations that could prevent and slow both tumour growth and spread.