Genetic biomarker identified for aggressive prostate cancer

MedWire News: The loss of a single nucleotide polymorphism located in the gene encoding the disabled homolog 2 interacting protein (DAB2IP) in prostate cancer cells may be responsible for cancer progression to other organs, show study findings.

The researchers observed that removing DAB2IP from human prostate carcinoma cells initiates epithelial-to-mesenchymal transition (EMT) which is a characteristic of metastatic cancer.

“Based on the outcome of this paper, we believe the assessment of DAB2IP in these cancer cells can be a valuable prognostic biomarker for risk of the aggressiveness of certain prostate cancers,” said lead author Daxing Xie, from the University of Texas Southwestern Medical Center, Dallas, USA.

The process of EMT, first observed in embryo development, allows generally immotile epithelial cells to convert to motile cells, and has recently been implicated in carcinoma invasion and metastasis, explain Xie and colleagues.

“The majority of human visceral tumors derived from carcinomas are primarily made up of epithelial cells,” said co-author Jer-Tsong Hsieh (China Medical University, Taichung, Taiwan). “When they acquire mesenchymal phenotypes, they lose cell-to-cell adhesion and become more mobile throughout the body.”

Previous studies have linked the DAB2IP gene with aggressive prostate cancer.

Xie and team investigated the functional role of DAB2IP in human prostate epithelial cells and prostate carcinoma cells, and found evidence of EMT indicated by repression of E-cadherin and up-regulation of vimentin after loss of DAB2IP.

When the researchers deleted DAB2IP from human prostate cancer cells in a human prostate xenograft mouse model, multiple lymph node and distant organ metastases developed. Conversely, when the researchers restored DAB2IP in metastatic prostate cancer cells, they found that the process of EMT was reversed, thus inhibiting cancer spread.

To assess the functionality of DAB2IP, the research team examined its effect on the GSK-3β- β-catenin signaling pathway. They report that DAB2IP appears to function as a “scaffold protein,” adjusting the activity of nuclear β-catenin/T-cell factor activity, and thereby regulating EMT.

“We believe that the assessment of DAB2IP expression in prostate cancer specimens can be a valuable prognostic biomarker for risk of prostate cancer metastasis, and the delineation of DAB2IP function could provide a potential intervention strategy for prostate cancer metastasis,” the team concludes in the journal Proceedings of the National Academy of Sciences of the USA.

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