Cancer Cell Biology and Signaling
Colleges & Departments:
College of Medicine, Department of Pharmacology and Nutritional Sciences
My lab studies oncogenic factors and pathways that drive disease progression and therapeutic resistance in colorectal cancer (CRC). We particularly focus on understanding the mechanistic basis of redundancy and crosstalk among oncoprotein-activated signaling pathways and how the functional crosstalk among these pathways promotes cancer progression and alters the therapeutic response to CRC. Through molecular analysis of mRNA translation states, our work establishes dysregulation of cap-dependent translation downstream of mTOR at the level of 4E-BP1/eIF4E, as a key to tumor formation, metastasis and resistance to upstream kinase-targeted therapies. Specifically, we identify 4E-BP1 as a critical node that integrates the oncogenic effects of the PI3K/AKT and RAS/RAF/MEK/ERK pathways in CRC progression. We employ a combination of molecular, cellular, biochemical, genetic, pharmacologic, imaging, bioinformatic, animal and clinical association approaches to decipher the transcriptional and post-transcriptional mechanisms controlling gene expression and pathways important for the malignant transformation and metastatic progression of CRC, with the ultimate goal of developing novel biomarkers and therapies for improving the diagnosis and treatment of this disease. In addition, we are also interested in developing nature product-based small molecular inhibitors for targeting translational control of CRC and potentially other major cancers.
- ERK and AKT signaling cooperate to translationally regulate survivin expression for metastatic progression of colorectal cancer. Ye Q, Cai W, Zhen Y, Evers BM, She QB. Oncogene 2013.
- Loss of 4E-BP1 function induces EMT and promotes cancer cell migration and invasion via cap-dependent translational activation of snail. Cai W, Ye Q, She QB. Oncotarget 5:6015-6027, 2014. PMCID: PMC4171609
- AKT inhibition overcomes rapamycin resistance by enhancing the repressive function of PRAS40 on mTORC1/4E-BP1 axis. Mi W, Ye Q, Liu S, She QB. Oncotarget 6:13962-13977, 2015. PMCID: PMC4546444
- Snail determines the therapeutic response to mTOR kinase inhibitors by transcriptional repression of 4E-BP1. Wang J, Ye Q, Cao Y, Guo Y, Huang X, Mi W, Liu S, Wang C, Yang HS, Zhou BP, Evers BM, She QB. Nat Commun 8:2207, 2017. PMCID: PMC5738350
- Frenolicin B targets peroxiredoxin 1 and glutaredoxin 3 to trigger ROS/4E-BP1-mediated antitumor effects. Ye Q, Zhang Y, Cao Y, Wang X, Guo Y, Chen J, Horn J, Ponomareva LV, Chaiswing L, Shaaban KA, Wei Q, Anderson BD, St Clair KD, Zhu H, Leggas M, Thorson JS, She QB. Cell Chem Biol 2018 Dec. 4. PubMed PMID: 30661989.