Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/36625
Title: FUNCTION AND MECHANISM STUDIES OF TRPV4 IN BREAST CANCER METASTASIS
Authors: CHOONG LEE YEE
Keywords: TRPV4, breast cancer, metastasis, calcium channel, AKT, E-cadherin
Issue Date: 28-Dec-2012
Source: CHOONG LEE YEE (2012-12-28). FUNCTION AND MECHANISM STUDIES OF TRPV4 IN BREAST CANCER METASTASIS. ScholarBank@NUS Repository.
Abstract: Transient Receptor Potential Vanilloid subtype 4 (TRPV4), a non-selective calcium-permeable cation channel was discovered by our laboratory to be a novel breast cancer metastasis-associated protein. TRPV4 was found to be upregulated in invasive breast cancer cell lines and tumor breast tissues. It has been shown that 4a-PDD induced activation of TRPV4 led to a rise in intracellular Ca2+ concentration. Our in-vitro studies indicated that silencing of TRPV4 significantly abolished the invasiveness and the ability of murine mammary breast cancer metastatic cells to transmigrate through endothelial cells, but not the proliferation of the cells. Furthermore, in-vivo studies demonstrated that knockdown of TRPV4 significantly reduced the number and size of metastatic nodules in the lungs of SCID mice. These effects of TRPV4 knockdown were associated with a reduction in the plasticity of the cancer cells and diminution of intracellular Ca2+ concentration. Interestingly, activation of TRPV4 led to Ca2+-dependent activation of AKT/ PI3K pathways and downregulation of cell adhesion proteins such as E-cadherin and ß-catenin, which may account for the decrease in cancer cell plasticity following TRPV4 knockdown. Our preliminary data showed that Twist might be involved in AKT-mediated repression of E-cadherin expression. Studies are currently under way in our laboratory to also investigate the potential role of proteosomal degradation in TRPV4-mediated downregulation of Ecadherin and ß-catenin. In conclusion, this study shows that TRPV4 plays a novel role in cellular processes associated with metastasis and provides insights into the mode of action of TRPV4 in metastasis.
URI: http://scholarbank.nus.edu.sg/handle/10635/36625
Appears in Collections:Master's Theses (Open)

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