Evaluation of the Potential Therapeutic Effect and Hormonal Regulation of the Endoplasmic Reticulum-Mediated Degradation Pathway (ERAD) in Breast and Prostate Cancer

Project no. 22791 · Status: Kapanmış · 2021

Summary

Breast cancer is the most common cancer type in women and prostate cancer is the most common cancer type in men and is one of the leading causes of cancer mortality. Steroid sex hormones play an important role in the initiation and spread of breast and prostate cancer. Due to the developing resistance to treatment in breast and prostate cancer, targeting different mechanisms and developing target-specific therapeutics has become important in recent years. In our project, the role of the quality control mechanism called Endoplasmic Reticulum Mediated Degradation Pathway (ERAD), which maintains proteostasis and sterol homeostasis in the cell, in breast and prostate cancer will be investigated. Inactivation of ERAD causes endoplasmic reticulum stress with the accumulation of misfolded proteins, and chronic stress activates cell death mechanisms by triggering various signaling pathways, especially the Unfolded Protein Response (UPR). On the other hand, in tumor cells, there is increased activation of ERAD, which reduces cellular stress in order to escape neoplasm growth and cell death. These make ERAD/UPR a powerful therapeutic target. In our project, 1.The regulation of ERAD components through estrogen and estrogen receptor in breast cancer will be investigated, 2.The possible effects and relationships of ERAD on estrogen and androgen receptors in breast and prostate cancer cell lines will be investigated with different approaches, 3.The effects of ERAD/UPR inhibitors causing 50% growth inhibition will be investigated. concentration will be determined, 4. The potential of the most active inhibitor as a candidate drug in breast and prostate cancer will be investigated with various functional experiments. With this study, estrogen regulation of ERAD will be examined for the first time in the literature. Additionally, there is no study on the effects of therapeutic candidate drug molecules using ERAD/UPR inhibitors on estrogen and androgen receptor levels and activity in breast and prostate cancer cells. Therefore, the results obtained from this study will make a significant contribution to the literature on molecular mechanisms that will enable more comprehensive diagnosis and treatment of breast and prostate cancer.

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