Dorraya El-Ashry, PhD
Dr. El-Ashry is an experimental pathologist who studies the tumor microenvironment and mechanisms of metastasis in breast cancer. Her current work is focused on the role of cancer-associated fibroblasts in the tumor microenvironment, circulation, and metastasis.
Cancer-associated fibroblasts (CAFs) are a novel population of fibroblasts, first identified by El-Ashry and colleagues, that are associated with the tumor cells in the breast cancer microenvironment. When breast cancer cells break free of the stromal-cell microenvironment and enter the bloodstream, they take components their microenvironment with them in the form of circulating CAFs (cCAFs). In preliminary studies El-Ashry found that cCAFs were more closely associated with breast cancer metastasis than circulating tumor cells (CTCs) from the primary tumor. El-Ashry and fellow investigators are exploring whether cCAFs alone or in conjunction with CTC allow for improved detection of early metastasis. If early results are extended and confirmed a liquid biopsy could be developed that serves as prognostic indicator for the disease.
El-Ashry is also investigating the basic mechanisms of breast cancer metastasis. When CAFs enter the bloodstream from the tumor microenvironment, they cluster with circulating tumor cells (CTCs). Her research team has found that the adhesion molecule CD44 is highly expressed in CAFs and facilitates cCAF-CTC clustering and co-migration to metastatic sites. She is collaborating with Jim McCarthy’s group, which has considerable experience with CD44 function in metastatic tumors. CD44 is also a marker for mesenchymal stem cells (MSCs), the progenitors of stromal cells, including fibroblasts, that constitute the breast cancer microenvironment. If CD44 is found to be critical for cCAF-CTC clustering, inhibiting its expression may disrupt the metastatic potential of breast cancer tumors and possibly other solid tumors that employ a comparable metastatic mechanism.
El-Ashry is working to develop novel methodologies for identifying, tracking, and targeting CAFs because she has found they play a primary role in driving cancer cell behavior – whether in the tumor microenvironment, in circulation, at metastatic sites, and possibly in setting up pre-metastatic niches for cancer cells from the primary tumor to take root.
Associate Professor, Department of Laboratory Medicine and Pathology
PhD, Experimental Biology, University of Colorado Health Sciences Center
BA, Molecular Biology, Vanderbilt University
Refereed journal articles
Kim M, Jang K, Miller P, Picon-Ruiz M, Yeasky TM, El-Ashry D, Slingerland JM. VEGFA links self-renewal and metastasis by inducing Sox2 to repress miR-452, driving Slug. Oncogene. 2017 Sep 7;36(36):5199-5211. doi: 10.1038/onc.2017.4. Epub 2017 May 15.
Kwak, T., Drews-Elger, K., Ergonul, A., Miller, P.C., Braley, A., Hwang, G.H., Zhao, D., Besser, A., Yamamoto, Y., Yamamota, H., El-Ashry, D., Slingerland, J.M., Lippman, M.E., and Hudson, B.I. Targeting RAGE-ligand Signaling Impairs Breast Cancer Cell Invasion and Metastasis. Oncongene, Sep 26 epub ahead of print, 2016.
Picon-Ruiz, M., Pan, C., Drews-Elger, K., Jang, K., Besser, A.H., Zhao, D., Morata-Terifa, C., Kim, M., Ince, T.A., Azzam, D.J., Wander, S.A., Wang, B., Ergonul, B., Datar, R.H., Cote, R.J., Howard, G.A., El-Ashry, D., Torne-Poyatos, P., Marchal, J.A. Slingerland, J.M. Cancer Research, Jan 15; 76(2): 491-504, 2016.
Hew K., Miller, P.C., El-Ashry, D., Sun, J., Besser, A.H., Ince, T.A., Gu, M., Zhang, G., Brafford, P.A., Guo, W., Lu, Y., Mills, G.B., Slingerland, J. A., and Simpkins, F. MAPK Activation Predicts Poor Outcome and the MEK Inhibitor, Selumetinib, Reverses Anti-Estrogen Resistance in High Grade Serous Ovarian Cancer. Clinical Cancer Research, Feb 15; 22(4); 935-947, 2016.
Ao, Z., Shah, S.H., Machlin, L.M., Parajuli, R., Miller, P.C., Rawal, S., Williams, A.J., Cote, R.J., Lippman, M.E., Datar, R.H., and El-Ashry, D. Identification of Cancer-Associated Fibroblasts in Circulating Blood from Patients with Metastatic Breast Cancer. Cancer Research, Nov 15; 75(22):4681-4687, 2015.
Shah, S.H., Miller, P., Contreras, M., Ao, Z., Machlin, L., Issa, E., and El-Ashry, D. Hierarchical Paracrine Interaction of Breast Cancer Associated Fibroblasts with Cancer Cells via hMAPK-microRNAs to Drive ER-Negative Breast Cancer Phenotype. Cancer Biology & Therapy, Oct 30; 16(11):1671-1681, July 2015.
Miller, P., Clarke, J., Koru-Sengul, T., Brinkman, J., and El-Ashry, D. A Novel MAPK microRNA Signature is Independently Predictive of Hormone Therapy Resistance and Poor Disease Outcome in ER- Positive Breast Cancer. Clinical Cancer Research, Jan 15; 21(2):373-385, 2015.
Cuiffo, B.G., Campagne, A., Bell, G.W., Lembo, A., Orso, F., Lien, E.C., Bhasin, M.K., Raimo, M., Hanson, S.E., Marusyk, A., El-Ashry, D., Hematti, P., Polyak, K., Mechta-Grigoriou, F., Mariana, O., Volinia, S., Vincent-Salomon, A., Taverna, D., and Karnoub, A.E. MSC-Regulated microRNAs Converge on the Transcription Factor FOXP2 and Promote Breast Cancer Metastasis. Cell Stem Cell, Dec 4; 15(6):762-774, 2014.
Drews-Elger, K., Iorns, E., Dias A., Ward T.M., Dean S.J., Clarke J., Miller P., Campion-Flora A., Nava-Rodrigues D., Reis-Filho J.S., Rae J.M., Thomas, D., Berry D., El-Ashry D., and Lippman M.E. Infiltrating S100A8+ Myeloid Cells Promote Metastatic Spread of Human Breast Cancer Growth and Predict Poor Patient Outcome. Breast Cancer Res Treat, Nov; 148(1):41-59, 2014.
Zhao, D., Pan C., Sun J., Gilbert C., Drews-Elger K., Azzam D., Picon-Ruiz M., Kim M., Ullmer W., El-Ashry D., Creighton C., and Slingerland J. VEGF Drives Cancer Initiating Cells Through VEGFR-2/Stat3 Signaling to Upregulate Myc and Sox2. Oncogene, Aug 25. doi: 10.1038/onc.2014.257, 2014.
Plotkin, A., Volmer C.-H., Wahlestedt C., Ayad N., and El-Ashry D. Transcriptional Repression of ER Through hMAPK-Dependent Histone Deacetylation by Class I HDACs. Breast Cancer Res Treat. Sep; 147(2):249-63, 2014.
Drews-Elger, K., Brinkman, J., Miller, P., Shah, S., Harrell, C., da Silva, T., Ao, Z., Schlater, A., Azzam, D., Diehl, K., Thomas, D., Slingerland, J., Perou, C., Lippman, M., and El-Ashry, D. Primary Breast Tumor-Derived Cellular Models: Characterization of Tumorigenic and Metastatic, and Cancer Associated Fibroblast Cultures. Breast Cancer Res Treat. Apr; 144(3):503-17, 2014.
Azzam, D.J., Drews-Elger, K., Zhao, D., Gilbert, C.A., Picon-Ruiz, M., Ranganathan, P., Han, Xiaoqing, H., Sun, J., Minn, A.J., Pan, C., Wander, S.A., Capobianco, A.J., El-Ashry, D., and Slingerland, J.M. Evidence for a Functional and Molecular Hierarchy in Tumor-Initiating Stem Cells in Triple-Negative Breast Cancer: Relevance to Metastasis and Therapy. EMBO Mol Med, 5(10):1502-1522, 2013.
Iorns, E., Drews-Elger, K., Ward, T.M., Dean, S., Clarke, J., El-Ashry, D., and Lippman, M.E. A New Mouse Model for the Study of Human Breast Cancer Metastasis. PlosOne, 7(10):e47995, 2012.
Bayraktar, U.D., Kim, T.K., Drews-Elger, K., Benjamin, C., El-Ashry, D., Wieder, E., and Komanduri, K.V. Simultaneous Measurement of ER, Her2, and PhosphoERK1/2 in Breast Cancer Cell Lines by Flow Cytometry. Breast Cancer Research and Treatment, 129(2):623-628, 2011.
Teschendorff, A.E., Gomez, S., Arenas, A., El-Ashry, D., Schmidt, M., Gehrmann, M., and Caldas, C. Improved Prognostic Classification of Breast Cancer Defined by Antagonistic Activation Patterns of Immune Response Pathway Modules. BMC Cancer, 10:604-624, 2010.
Hnatyszyn, J., Lui, M, Hilger, A., Herbert, L., Gomez-Fernandez, C.R., Jorda, M., Thomas, D., Rae, J.M., El-Ashry, D., and Lippman, M.E. Correlations between GREB1 expression and ER, HER2 status in human breast cancer. Breast Cancer Research and Treatment, 122:371-380, 2009.
Bayliss, J., Hilger, A., Vishnu, P., Diehl, K., and El-Ashry, D. Reversal of the Estrogen-Negative Phenotype and Restoration of Anti-Estrogen Response in Breast Cancer. Clinical Cancer Research, 13: 7029-7036, 2007.
19. Creighton, C., Hilger, A., Murthy, S., Rae, J., Chinnaiyan, A., and El-Ashry, D. Activation of MAPK in ER?-positive breast cancer cells in vitro induces an in vivo molecular phenotype of ER?-negative human breast tumors. Cancer Research, 66(7):3903-3911, 2006.