Breast cancer is the most diagnose cancer in women. The adenoviral type 5 E1A (E1A) associates with multiple anti-cancer activities and has been tested in multiple clinical trials in a gene therapy setting for breast, ovarian and head and neck cancer patients. Many studies showed that E1A involves in several anti-cancer abilities such as inhibit tumor progression, increase chemo-drugs sensitization and metastasis suppression. Metastasis is the main cause of death for cancer patients, including breast cancer patients. Biological significances of E1A in suppression of cancer progression urgent us to clarify the detail molecular mechanisms of E1A’s anti-cancer activity. Therefore, we are interest in understand the molecular mechanisms that associate with E1A-mediated inhibition of cancer metastasis for potentially improve the clinical trials of breast cancer patients in the future. In our preliminary results, E1A significantly suppressed the expression of Glucose-regulated protein 78 (GRP78), a chaperone protein which has been widely reported that associates with malignancy and metastasis of various types of cancer. The goal of this project is to understand the biological function and regulatory mechanisms of GRP78 in E1A-inhibited metastasis. To reach this goal, we will focus on how E1A regulate the expression of GRP78 and exert suppressive activity of cancer metastasis in breast cancer. Following four specific aims will help us to reveal the goal. SPECIFIC AIM 1: To define the role of GRP78 in E1A-mediated inhibition on cancer cell migration/invasion. SPECIFIC AIM 2: To reveal the molecular mechanisms involved in the regulation of GRP78 by E1A. SPECIFIC AIM 3: To study the biological significance of GRP78 in E1A-mediated metastasis suppression in animal model. SPECIFIC AIM 4: To investigate the clinical significance of GRP78 and related signal molecules in breast cancer patients. Achievements of these specific aims will help us to establish signaling networks to understand better the molecular mechanisms of E1A-mediated inhibition of cancer metastasis. Furthermore, the findings from this project may provide more potential targets to develop novel anti-cancer therapeutic strategies.
|Effective start/end date||8/1/15 → 7/31/16|
- Adenoviral type 5 E1A (E1A)
- Glucose-regulated protein 78 (GRP78)
- Cancer metastasis