The Role of the Cellular Stress Program for Prostate Cancer Cells to Grow in the Bone Microenvironment
Abstract
Tumors face many stresses such as starvation, low oxygen levels, and treatment-induced cell death. During metastasis, cells face even more stresses as they break away from the primary tumor and invade into the surrounding cells and enter the circulation and survive in the blood stream. In the blood stream or lymph vessel, they must resist cell death associated with the loss of cellular contact, evade immune recognition, and survive physical stresses before arriving at a distant site. Then, the cells must either leave or proliferate within the vessel and finally establish themselves and survive in a new environment at a foreign tissue site, such as the bone for prostate cancer, by invading the tissue and growing new blood vessels to obtain nutrients and oxygen. The cells that adapt to metastasize must employ a stress response pathway. Under stress conditions, cells downregulate protein synthesis globally and use an alternate mechanism to translate proteins required to cope with the stress. This proposal aims to prevent cells from employing the alternate stress response pathway of protein synthesis in order to impair the ability of the cells to survive under stress. This leads to the hypothesis that tumors capable of metastasizing and surviving in the bone microenvironment are dependent upon the alternative mechanism of translation for survival and invasion in the bone. The proposed studies will address the Prostate Cancer Research Program (PCRP) overarching challenge to develop effective treatments and address mechanisms of resistance for men with metastatic prostate cancer by establishing whether the alternate translation pathway is required for bone metastasis. The survival pathway would be critical for tumor cells to resist cell death induced by current treatments. These studies will address important PCRP focus areas to better understand the molecular mechanisms required for prostate cancer to metastasize to the bone and identify a new target for development of a therapeutic for bone metastases.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510483
Entities
People
- Sunnie R Thompson
Organizations
- United States Army
- University of Alabama at Birmingham