Binhua P Zhou, MD, PhD
Connect
859-323-4474peter.zhou@uky.edu
Positions
- Professor
- Madeline F. James & Edith D. Gardner Endowed Chair
- Co-director, Center For Cancer and Metabolism
- Co-leader, MCO Program, Markey Cancer Center
College Unit(s)
Other Affiliation(s)
- Markey Cancer Center
Biography and Education
Education
MD, Clinical Medicine, Guangzhou Medical University, China
PhD, Neuroscience, University of Texas at Austin
Post-doc, Breast Cancer Research, University of Texas MD Anderson Cancer Center
Research
Metastasis, the spread of cells from a primary tumor to distant sites, is the main cause of death in patients with cancer. Epithelial-mesenchymal transition (EMT), a process vital for morphogenesis during embryonic development, is attracting increasing attention from oncologists as a potential mechanism for the initial step of metastasis. Many genes implicated in EMT during embryogenesis are being discovered, one after another, to control metastasis. We are currently focusing on characterization of the functional role and regulation of Snail/Slug transcription factors in the control of EMT. Snail and Twist are key transcriptional factors that were identified in Drosophila as EMT inducers in the control of embryogenesis. Flies and mice without either Snail or Twist are lethal because of severe defects at the gastrula stage during development. Expression of Snail and Twist correlate with the tumor grade and nodal metastasis of many types of tumor and predicts a poor outcome in patients with metastatic cancer. We are employing biochemical, molecular, and cellular approaches to study the functional regulation of Snail and Twist in breast cancer and will apply the knowledge that we gained for the prevention, diagnosis, and treatment of metastatic breast cancer in a long run. The goal of our research program is to uncover altered signaling pathways that regulate metastasis in cancer and, by discovery these pathways, to identify molecules that may serve as the therapeutic targets for metastasis prevention.
Selected Publications
1. Zhou BP, Liao Y, Xia W, Spohn B, Lee MH, and Hung MC. Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells, Nature Cell Biology 3:245-252, 2001
News and Views: El-Deiry WS. Akt takes centre stage in cell-cycle deregulation. Nature Cell Biology 3: E1-E3, 2001
2. Zhou BP, Liao Y, Xia W, Zou Y, Spohn B, Hung MC. HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation. Nature Cell Biology 3:972-982, 2001
Highlights: Brooksbank C. Oncogenes, Breaking and Entering. Nature Review Cancer 1: 96, 2001
3. Deng J, Miller SA, Wang HY, Xia W, Wen Y, Zhou BP, Li YM, Lin SY, Hung MC. β-Catenin interacts with and inhibits NF-κB in breast and colon cancer cells. Cancer Cell 2:323-334, 2002
4. Li YM, Pan Y, Wei Y, Cheng X, Zhou BP, Tan M, Zhou X, Xia W, Hortobagyi GN, Yu D, Hung MC. Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis, Cancer Cell 6:459-469, 2004
Preview: Benovic JL and Marchese A. A new key in breast cancer metastasis. Cancer Cell 6:429-430, 2004
News and Views: Eccles SA. and Paon L. Breast cancer metastasis: when, where, how? Lancet 365:1006-1007, 2005
5. Zhou BP, Deng J, Xia W, Xu J, Li YM, Gunduz M, Hung MC. Dual regulation of Snail by GSK-3β-mediated phosphorylation in control of epithelial-mesenchymal transition. Nature Cell Biology 6:931-940, 2004
News and Views: Schlessinger K and Hall A. GSK-3β sets Snail’s pace. Nature Cell Biology 6: 913-915, 2004
6. Cha TL, Zhou BP, Xia W, Wu Y, Yang CC, Chen CT, Ping B, Otte AP, and Hung MC, Akt-mediated phosphorylation of EZH2 suppresses methylation of lysine 27 in histone H3, Science 310:306-310, 2005
7. Wu Y, Deng J, Rychahou PG, Qiu S, Evers BM, and Zhou BP, Stabilization of Snail by NF-κB Is Required for Inflammation-Induced Cell Migration and Invasion, Cancer Cell 15(5):416-28, 2009
Featured Article of May 2009 issue of Cancer Cell with commentary from: Preview: Yang CC, Wolf DA. Inflamed snail speeds metastasis. Cancer Cell 15(5):355-7, 2009
Leading Edge: Smith OM, Metastasis proceeds at more than a Snail’s pace, Cell 137, 591, 2009
Nature Cell Migration Gateway: Baumann K, Inflammation-induced metastasis: Moving at a Snail's pace, June 2009
8. Lin Y, Wu Y, Li J, Dong C, Ye X, Chi Y.-I, Evers BM, and Zhou BP, The SNAG Domain of Snail1 Functions as a Molecular Hook for Recruiting Lysine-specific Demethylase 1, EMBO J 29(11):1803-16, 201
Commentary Coverage: Christofori G, Snail1 links transcriptional control with epigenetic regulation, EMBO J 29(11):1787-1789
9. Dong C, Wu Y, Yao J, Wang Y, Yu Y, Rychahou PG, Evers BM, and Zhou BP, G9a Interacts with Snail and is Critical for Snail-mediated E-cadherin Repression in Breast Cancer, Journal of Clinical Investigation 122(4):1469-86, 2012
10. Dong C, Yuan T, Wu Y, Wang Y, Fan TW, Miriyala S, Lin Y, Yao J, Shi J, Kang T, Lorkiewicz P, St Clair D, Hung MC, Evers BM, and Zhou BP, Loss of FBP1 by Snail-mediated Repression Provides Metabolic Advantages in Basal-like Breast Cancer, Cancer Cell 23(3):316-331, 2013
Preview: Schieber MS and Chandel NS, ROS Links Glucose Metabolism to Breast Cancer Stem Cell and EMT Phenotype, Cancer Cell 23(3):265-267, 2013
Voted as #2 of top10 best papers in Cancer Cell 2013
11. Wu Y, Wang Y, Yang XH, Kang TB, Zhao Y, Wang C, Evers BM, and Zhou BP, Deubiquitinase USP28 Confers Breast Cancer with Stem Cell-like Traits by Stabilizing LSD1, Cell Reports 5(1):224-36, 2013
12. Shi J, Wang Y, Zeng L, Wu Y, Deng J, Zhang Q, Lin Y, Li J, Kang TB, Tao M, Rusinova E, Zhang GT, Wang C, Zhu H, Yao J, Zeng YX, Evers BM, Zhou MM, Zhou BP, Disrupting the Interaction of BRD4 with Di-acetylated Twist Suppresses Tumorigenesis in Basal-like Breast Cancer, Cancer Cell 10;25(2):210-25, 2014
Voted as #4 of top 8 best papers in Cancer Cell 2014
13. Zhang D, Wang Y, Shi Z, Liu J, Sun P, Hou X, Zhang J, Zhao S, Zhou BP*, and Mi J*, Metabolic reprogramming of cancer-associated fibroblasts by IDH3α downregulation, Cell Reports 10(8):1335-48, 2015
14. Wu Y, Wang Y, Lin Y, Liu Y, Wang Y, Jia J, Singh P, Chi Y-I, Wang C, Dong C, Li W, Tao M, Napier D, Shi Q, Deng J, Evers BM, and Zhou BP, Dub3 Inhibition Suppresses Breast Cancer Invasion and Metastasis by Promoting Snail1 Degradation, Nature Communications 8:14228, 2017
15. Wang J, Ye Q, Cao Y, Guo Y, Huang X, Mi W, Liu S, Wang C, Yang H.-S., Zhou BP, Evers BM, She Q.-B, Snail determines the therapeutic response to mTOR kinase inhibitors by transcriptional repression of 4E-BP1, Nature Communications 8(1):2207, 2017
16. Liu J, Duan Z, Guo W, Zeng L, Wu Y, Chen Y, Tai F, Wang Y, Lin Y, Zhang Q, He Y, Deng J, Stewart RL, Wang C, Lin PC, Ghaffari S, Evers BM, Liu S, Zhou MM, Zhou BP*, Shi J*, Targeting the BRD4/FOXO3a/CDK6 axis Sensitizes AKT Inhibition in Luminal Breast Cancer, Nature Communications 9(1):5200, 2018
17. Xiong G, Chen J, Zhang G, Wang S, Kawasaki K, Zhu J, Zhang Y, Nagata K, Li Z, Zhou BP, Xu R, Hsp47 promotes cancer metastasis by enhancing collagen-dependent cancer cell-platelet interaction, Proc Natl Acad Sci USA 117(7):3748-3758, 2020
18. Yang J, Antin P, Berx G, Blanpain C, Brabletz T, Bronner M, Campbell K, Cano A, Christofori A, Dedhar S, Derynck R, Ford HL, de Herreros AG, Goodall G, Hadjantonakis AK, Huang R, Kalcheim C, Kalluri R, Kang Y, Khew-Goodal Y, Levine H, Liu J, Longmore GD, Mani SA, Massagué J, Mayor R, McClay D, Newgreen DF, Nieto MA, Puisieux A, Runyan R, Savagner P, Stanger B, Stemmler M, Takahashi Y, Thiery JP, Thompson EW, Weinberg RA, Williams E, Xing J, Zhou BP, Sheng G, Definitions and Guidelines for Research on Epithelial-Mesenchymal Transition, Nature Review Molecular Cell Biology 21(6):341-352, 2020