Grant: Master's Award: Canada Graduate Scholarships

Mechanistic target of rapamycin (mTOR) is a complex central hub for various signaling pathways regulating protein synthesis, cellular differentiation, proliferation and transformation. mTOR is activated upon phosphorylation of its serine 2448 (pS2448) residue which is a rapamycin sensitive site. Recently Shrivastav et al (Breast Cancer Research, 2014) reported that activated mTORC1 (pS2448 mTOR, determined by immunohistochemistry) in a cohort of more than 300 estrogen receptor (ER) positive breast cancer cases is positively correlated with better clinical outcome in patients subsequently treated with tamoxifen. In preliminary research at Dr. Shrivastav’s laboratory indicates N-myristoyltransferase (NMT1) is regulated by mTORC1, which in turn regulates activity of c-Src. Phosphorylation of ERa on tyrosine residue 537 (p ERa Y537) is aided by c-Src. Phosphorylated ERa on Y537 in primary breast cancer predicts poor OS and RFS when patients are later treated with Tamoxifen. Therefore the overreaching goal of this study is to investigate the mechanistic relationship between ERa/mTOR/NMT1 pathways that will shed light on breast cancer progression and simultaneously identify molecular markers that can serve both as prognostic markers and therapeutic targets.