Regulation of HIF-1-Alpha, miR-200, and Markers of Cancer Stem Cells by CDF Under Hypoxic Condition
Final rept. 1 Apr 2011-31 Mar 2012
WAYNE STATE UNIV DETROIT MI
Pagination or Media Count:
Prostate Cancer PCa is the most commonly diagnosed cancer in men and is the second leading cause of cancer death in the USA 1. Most PCa patients are treatable, but the patients usually die due to drug resistance and metastatic disease. Thus, there is a dire need for the development of novel strategies by which drug resistance and metastatic disease could be controlled with novel agents with better treatment outcome. Hypoxia is one of the fundamental biological phenomena that are intricately associated with the development and aggressiveness of a variety of solid tumors including PCa. Hypoxia-inducible factors HIF function as a master transcription factor, which regulates hypoxia responsive genes and have been recognized to play critical roles in tumor invasion, metastasis, and chemo-radiation resistance, and contributes to increased cell proliferation, survival, angiogenesis and metastasis 2, 3. Therefore, tumor hypoxia with deregulated expression of HIF and its biological consequence lead to poor prognosis of patients diagnosed with solid tumors, resulting in higher mortality, suggesting that understanding of the molecular relationship of hypoxia with other cellular features of tumor aggressiveness would be invaluable for developing newer targeted therapy for solid tumors. It has been well recognized that cancer stem cells CSCs and epithelial-to-mesenchymal transition EMT phenotypic cells are associated with therapeutic resistance and contributes to aggressive tumor growth, invasion, metastasis, and are believed to be the cause of tumor recurrence 4. Emerging evidence suggest that hypoxia and HIF pathway enhance the phenotypes and functions of CSC and EMT 5-9, contributing to tumor aggressiveness, which could also be due to deregulation of microRNAs miRNAs.
- Anatomy and Physiology
- Medicine and Medical Research