Binhua P. Zhou

Bio / Education: 

M.D., Guangzhou Medical University, 1986
Ph.D., University of Texas, Austin, 1996
Post-doctoral training, MD Anderson Cancer Center, 1997-2001

Research Description: 

Breast cancer is the most common cancer in women. The clinical symptoms and outcome of breast cancer depend largely on whether it is confined to the breast or has spread to adjacent or distant parts of the body. Despite more than 3 decades of research, approximately 90% of breast cancer deaths are caused by local invasion and distant metastasis of tumor cells, and the average time to live after documentation of metastasis is approximately 2 years. EMT is a vital process for large scale of cell movement during the morphogenesis at embryonic development.

In this EMT event, cells change from “static” to “motile” in appearance and start to migrate. This is because the cell-cell adhesion molecule E-cadherin is lost, and cells break away from one other and start to migrate and invade the surrounding tissue. Tumor cells usurp this developmental process for their invasion and metastasis. The major challenge in breast cancer research is to identify the factors within the cell and the signals outside the cell that initiate this early event of metastasis.

Snail is a zinc-finger transcriptional repressor in controlling EMT during embryogenesis and metastasis. Expression of Snail correlates 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 in breast cancer and, by discovery dis-regulations, 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, and 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-kB 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, and 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, and 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 Is Required for Inflammation-Induced Cell Migration and Invasion, Cancer Cell, 15(5):416-28, 2009 (Featured Article of May 2009 issue)
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, 2010
Commentary Coverage: Christofori G, Snail1 links transcriptional control with epigenetic regulation, EMBO J, 29(11):1787-1789, 2010

(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

(11) Wu Y, Wang Y, Yang YH, Kang T, 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, 25(2):210-225, 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 YI, Wang C, Dong C, Li W, Tao M, Napier D, Shi Q, Deng J, Mark Evers B, Zhou BP*, Dub3 inhibition suppresses breast cancer invasion and metastasis by promoting Snail1 degradation, Nature Communications. 2017 Feb 15;8:14228