Prostate cancer cells more likely to spread with specific gene function loss

Washington, Feb 3 (ANI): A new research has shown that prostate cancer cells are more likely to spread to other parts of the body if a specific gene quits functioning normally.

Certain prostate cancer cells can be held in check by the DAB2IP gene. The gene's product, the DABIP protein, acts as scaffolding that prevents many other proteins involved in the progression of prostate cancer cells from over-activation.

However, when those cells lose the DAB2IP protein, they break free and are able to metastasize, or spread, drastically increasing the risk of cancer progression in other organs as the cells travel through the bloodstream or lymph system.

The study in mice found that eliminating the DAB2IP scaffolding in human carcinoma cells caused them to change from epithelial cells to mesenchymal cells - a hallmark of metastatic cancer.

"Cells undergoing an epithelial to mesenchymal transition (EMT) experience biological changes that enable them to move freely and spontaneously throughout the body," said Dr. Jer-Tsong Hsieh, from UT Southwestern Medical Center and the study's senior author.

"By restoring DAB2IP function in cancer cells in mice, we reversed their ability to change and metastasise," Hsieh added.

Hsieh said that identifying the DAB2IP protein in human cells might serve as a biomarker, helping physicians identify patients who could have more aggressive, metastatic forms of prostate cancer.

EMT is known to play an important role in embryo implantation, embryogenesis and organ development, and tissue regeneration, as well as in cancer progression and metastasis. For cancer progression, EMT is believed to facilitate the migratory and invasive ability of cancer cells.

"Carcinoma cells undergo several changes that enable them to spread. The majority of human visceral tumours derived from carcinomas are primarily made up of epithelial cells. When they acquire mesenchymal phenotypes, they lose cell-to-cell adhesion and become more mobile throughout the body," Hsieh said.

In the current study, Dr. Hsieh and his team first shut down the DAB2IP gene expression in prostate epithelial cells in mice and found that the prostate cancers did indeed metastasize to lymph nodes and other organs in mice.

When the researchers restored the DAB2IP genetic function to metastatic prostate cancer cells, the EMT process reversed, thereby inhibiting the cancer cells' ability to spread.

The study has been published in the Jan. 11 issue of the Proceedings of the National Academy of Sciences. (ANI)