Department of Pathology

Department Faculty

Rachel Hazan, Ph.D.

Dr. Rachel Hazan
 

Professional Interests

Cell-cell adhesion is a primary modulator of morphogenetic events during normal embryonic development. Metastatic dissemination of epithelial tumor cells is also strongly influenced by the activity of cell-cell adhesion molecules, in particular members of the cadherin family. My laboratory has shown that N-cadherin, a cadherin involved in dynamic processes such as cell migration and neurite outgrowth, is upregulated in invasive breast cancer cells and promotes metastasis of breast cancer cell lines. In contrast, E-cadherin, known to promote stable epithelial contacts, is lost during metastatic progression. Our data suggest that cadherin switching during tumor progression has a broader consequence than a simple change in cell-cell adhesion. The shift in cadherin expression also affects proteolytic activity of cells, their migration, invasiveness and metastasis. We and others have shown that even in the presence of E-cadherin, and strong cell-cell adhesiveness, N-cadherin can convert poorly invasive breast cancer cell lines into invasive and metastatic tumors, thus suggesting a dominant role for N-cadherin in this process. These effects of N-cadherin are mainly due to a functional cooperation with the FGF receptor resulting in epithelial to mesenchymal transition, cell signaling and morphological changes leading to metastasis. Thus our hypothesis is that N-cadherin upregulation in tumor cells is a key step in a series of interdependent molecular changes which lead to metastasis. 

More recently, we discovered that Retinal cadherin (R-cadherin), a classic cadherin highly expressed in the brain and retina is also present in the mammary epithelium. We showed that similarly to E-cadherin, R-cadherin acts as an invasion suppressor gene which is downregulated in invasive duct carcinomas. Moreover, R-cadherin knockdown in mammary gland tissue leads to disruption of morphogenesis and gain of metastastic properties. Conversely, R-cadherin expression in aggressive tumor cells suppresses invasion and metastasis, and restores glandular morphogenesis. 

My laboratory is currently investigating: 1) the molecular basis for cooperation between N-cadherin and the FGF receptor responsible for epithelial to mesenchymal transition (EMT) and metastasis with the goal of obtaining functional inhibitors of metastasis. 2) Regulation of EMT and metastasis by the MAPK and AKT signaling pathways 3) the relationship between cell cycle progression and tumor metastasis. 4) The mechanism of HER2 therapeutic resistance in breast cancer. 5) Cancer stem cells and their role in breast cancer metastasis.
 

Lab Members

Kimita Suyama, PhD
Associate
kimita.suyama@einstein.yu.edu
718.430.3374

Jiahong Yao, MD
Associate
jiahong.yao@einstein.yu.edu
718.430.3374

Yulong Zhou, PhD
Visiting Scientist
email pending
718.430.3374

 

 

Selected Publications

Hazan, R.B., Phillips, G.R., Qiao, R.F., Norton, L. and Aaronson, S.A. (2000). Exogenous expression of Ncadherin in breast cancer cells induces cell migration, invasion and metastasis. J. Cell Biol.148: 779-789. PMID: 10684258

Suyama, k., Shapiro I., Guttman, M., and Hazan, R.B (2002) A signaling pathway leading to metastasis is controlled by N-cadherin and the FGF receptor. Cancer Cell. 2: 301-314. PMID: 12398894

Nagi C, Guttman M, Jaffer S, Qiao R, Keren R, Triana A, Li M, Godbold J, Bleiweiss IJ, Hazan R (2005). Ncadherin expression in breast cancer: correlation with an aggressive histologic variant-invasive micropapillary carcinoma. Breast Cancer Res & Treat. 94:225-232. PMID: 16258702

Triana A, Sen C, Wolfe D, and Hazan R (2005). Cadherins and catenins in clival chordomas: correlation of expression with tumor aggressiveness. Am J Surg Pathol .29:1422-1434. PMID: 16224208

Cohen I, Pappo O, Elkin M, San T, Bar-Shavit R, Hazan R, Peretz T, Vlodavsky I, Abramobitz, R. (2006) Heparanase promotes growth, angiogenesis, and survival of primary breast tumors. Int J Cancer.18:1609-17. PMID: 16217746

Hulit J, Suyama k, Chung S, Keren R, Agiostratidou G, Shan W, Dong X, Williams TM, Lisanti MP, Knudsen K, Hazan RB (2007). N-cadherin signaling potentiates mammary tumor metastasis via enhanced ERK activation. Cancer Res. 67:3106-16. PMID: 17409417

Agiostratidou, G, Li, M, Suyama, K., Keren, R, Chung, S, Badano.I , Qian, K., Hulit, J., Boumediene,B., Loudig, O., Phillips, G, Locker, J and Hazan, RB (2009).  Loss of R-cadherin facilitates breast tumor progression and metastasis. Cancer Res. 69:5030-38. PMID: 1949127

Chung, S., Yao, J., Suyama, K., Bajaj, S., Qian, X., Loudig, O., Eliseo, E., Phillips, G., Hazan. R.B. (2013). Ncadherin promotes breast cancer cell migration through Akt3 suppression. Oncogene. 32(4):422-30. PMID:22410780

Qian, X., Hulit, J., Suyama, K., Belbin, T., Smirnova, T., Segall, J., Phillips, G., Norton L., Hazan. R.B. (2013). p21 CIP mediates reciprocal switching between proliferation and invasion during metastasis. Oncogene. 2012 Jul 2. PMID: 22751124

Kotorashvili, A., Ramnauth A., Liu, C., Lin, J., Ye, K., Kim, RS., Hazan, R., Rohan, T., Fineberg, S., Loudig, O. (2012). Effective DNA/RNA co-extraction for analysis of microRNAs, mRNAs, and genomic DNA from formalinfixed paraffin-embedded specimens. PLoS One. 7(4). PMID: 22514653

Hou, J., Rodriguez-Gabin, G., Samaweera, L., Hazan, R., Goldberg, G., Horwitz, SB., McDaid, H. (2012). Exploiting MEK Inhibitor- Mediated Activation of ERα for Therapeutic Intervention in ER-Positive Ovarian Carcinoma. PLoS One. 8(2). PMID: 23390495

Qian X, Anzovino A, Hulit J, Kim S , Suyama K, Chandiramani N, McDaid HM, Nagi C, Phillips GR, Norton L,Hazan RB. (2013). N-cadherin/FGFR Signaling Promotes Epithelial to Mesenchymal Transition and Tumor Initiating Potential in ErbB2-driven Breast Cancer. Oncogene. PMID: 23975425

Kim S, Yao J, Suyama K, Qian X, Qian BZ, Bandyopadhyay S, Loudig OD, De Leon-Rodriguez C, Zhou ZN, Segall JE, Macian F, Norton L, Hazan RB. (2014). Slug Promotes Survival during Metastasis through Suppression of Puma-Mediated Apoptosis. Cancer Research. PMID: 2483072

Jiang H, English BP, Hazan RB, Wu P, Ovryn B. (2015). Tracking surface glycans on live cancer cells with single-molecule sensitivity. Angew Chem Int Ed Engl. 2015 PMID: 25515330

 

 

More Information About Dr. Rachel Hazan

Department of pathology

Keywords

Adhesion, Cadherin, Signaling, EMT, Metastasis

Material in this section is provided by individual faculty members who are solely responsible for its accuracy and content.

Contact

Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Forchheimer Building, Room 529S
Bronx, NY 10461

Tel: 718.430.3349
Fax: 718.430.8541
rachel.hazan@einstein.yu.edu

 
Pubmed Search
Collexis Research Profiles
Einstein Research Profiles (ERP) is one of the innovative technologies to create collaborative bridges within and across the entire bench-to-bedside-to-population spectrum of research. The ERP website has been developed in partnership with Collexis to give investigators easy access to PubMed publications, coauthor networks, information about NIH grants, and research networks.

Additional Information

Summary:

Mechanisms of Breast Cancer Metastasis.

Education:

Institute: Weizman Institute of Science, Israel
Year: 1979
Major: Immunology
Degree: MSc

Institute: George Washington University
Year: 1989
Major: Cell Biology, Molecular Biology
Degree: Ph.D

Institute: Rockefeller University, NY &Scripps Research Institute, La Jolla, CA
Year: 1990-1994
Major: Cell Biology, Molecular Biology
Degree: Post-doctoral studies

Biosketch or CV