Binhua P Zhou, MD, PhD
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Professor
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Madeline F. James & Edith D. Gardner Endowed Chair
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Co-director, Center For Cancer and Metabolism
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Co-leader, MCO Program, Markey Cancer Center
Contact
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
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
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
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
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
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
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
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
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
19. Xiao J, Wang J, Li J, Xiao J, Liu C, Tan L, Tu Y, Yang R, Pei Y, Wang M, Wong J, Zhou BP, Li J, Feng J, L3MBTL3 and STAT3 collaboratively upregulate SNAIL expression to promote metastasis in female breast cancer, Nature Communications 16(1): 231, 2025
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
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
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
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
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
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
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
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
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
19. Xiao J, Wang J, Li J, Xiao J, Liu C, Tan L, Tu Y, Yang R, Pei Y, Wang M, Wong J, Zhou BP, Li J, Feng J, L3MBTL3 and STAT3 collaboratively upregulate SNAIL expression to promote metastasis in female breast cancer, Nature Communications 16(1): 231, 2025
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