Friday, June 13, 2008

The TAZmanian Devil

TAZ (transcriptional co-activator with PDZ-binding motif), also called WWTR1 (WW domain-containing transcription regulator 1), is known to regulate the differentiation of mesenchymal stem cells. Upon analyzing the proteins in human cancer cell lines, the level of expression of TAZ has been found to be higher in more invasive breast cancer cells, suggesting a correlation between the level of expression of TAZ in human breast cancer cell lines and the invasiveness of the cancer cells. This led to the investigation of the role of TAZ in the tumorigenesis of breast cancer.

The proposed mechanism of action of TAZ overexpression in breast cancer cells was based on the fact that invasiveness of cancer cells is dependent on increased migratory and invasive properties. The overexpression of TAZ has been shown to induce cell transformation and enhance cell migration and invasion through the wound-healing and Transwell assays. By causing a morphologic change from an epithelial to a fibroblast-like appearance thereby triggering the loss of epithelial property in order to promote the migratory property of the cells, it can be said that TAZ is a negative regulator of epithelial morphology and a positive regulator for invasive and migratory behavior. This event is significant for the progression of ductal carcinoma in situ into IDC (invasive/infiltrating ductal carcinoma).

The finding in this study highlights the role of TAZ in the tumorigenesis of breast cancer cells. The mechanism of action includes triggering the loss of epithelial morphology, promoting cell migration and invasion, and supporting anchorage-independent growth, all three of which are important for cancer initiation, progression, and invasion.

Because TAZ plays a significant role in the tumorigenesis of breast cancer cells, it might serve useful for the detection and treatment of breast cancer. With the existing correlation between its level of expression and breast cancer cell invasiveness, TAZ might offer a novel and effective target for breast cancer therapy.

Future studies are needed for additional insights, particularly in the elucidation of the mechanism of TAZ at the molecular level regarding its role in breast cancer cell migration, invasion, and tumorigenesis.

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