Cancer Institute

  • Azeddine Atfi

    atfi_azeddine.jpgProfessor, Department of Biochemistry
    Tumor Cell Biology Program
    Director, Tumor Cell Biology Program
    PhD, Molecular and Cellular Biology, 1992, Rennes University, France
    Postdoc, 1993-95, McGill University, Montreal Canada

    Contact information
    2500 N State St, Suite G651-04
    Laboratory, G756
    Jackson, MS 39216
    Phone: (601) 815-6831
    Fax: (601) 815-6806

    Research interests

    • Molecular characterization of PHRF1, a novel tumor suppressor
    • Role of the homeodomain protein TGIF in melanoma
    • Role of TGIF in bone formation

    Research synopsis

    My research is aimed at elucidating the interactions between signaling pathways as well as understanding their roles in human diseases. Our research projects include:

    • TGF-β and cancer: TGF-β controls critical events in metazoan development, and disruption of its activity has been implicated in cancer. TGF-β signaling is negatively regulated by the homeodomain protein TGIF. Recently, we identified PHRF1 as an ubiquitin ligase that triggers TGIF degradation, and thereby promotes TGF-β signaling. Since the PHRF1 gene localizes to the locus 11p15.5, which is frequently deleted in human tumors, we are interested in investigating whether PHRF1 could function as a tumor suppressor, focusing on breast cancer and melanoma.
    • TGIF and melanoma: Melanoma is one of the most aggressive neoplasms and a leading cause of skin cancer associated-death. We found that genetic deletion of TGIF in mice resulted in spontaneous melanoma. In addition, we found that TGIF can promote Wnt signaling, which plays an important role in melanoma progression. Accordingly, another ongoing project is to investigate whether TGIF promotes melanoma by enforcing activation of Wnt signaling.
    • TGIF and bone formation: Skeletal homeostasis depends on a higher-order network that balances bone formation by osteoblasts with bone resorption by osteoclasts. Perturbations of this network are often associated with skeletal disorders. Several solid and hematopoietic malignancies metastasize to the bone and disrupt bone homeostasis. One important regulator of bone formation is Wnt signaling. Since our data show that TGIF can promote Wnt signaling, another research project of the laboratory is to investigate whether TGIF could regulate bone formationhomeostasis.

    Selected publications

    • Dietary pterostilbene is a novel MTA1-targeted chemopreventive and therapeutic agent in prostate cancer. Dhar, Kumar, Zhang, Rimando, Lage , Lewin, Atfi, Zhang, Levenson. Oncotarget. 2016 Mar 1. doi: 10.18632/oncotarget.7841
    • TGIF function in oncogenic Wnt signaling. Razzaque MS, Atfi A. Biochim Biophys Acta. 2016 Apr;1865(2):101-4. doi: 10.1016/j.bbcan.2015.10.003. Epub 2015 Nov 11. Review. PMID:26522669
    • AKT and 14-3-3 regulate Notch4 nuclear localization. Ramakrishnan G1, Davaakhuu G1, Chung WC1, Zhu H1, Rana A2, Filipovic A3, Green AR4, Atfi A5, Pannuti A5, Miele L1, Tzivion G5. Sci Rep. 2015 Mar 5;5:8782. doi: 10.1038/srep08782.
    • Disruption of the PHRF1 Tumor Suppressor Network by PML-RARα Drives Acute Promyelocytic Leukemia Pathogenesis. Prunier C1, Zhang MZ2, Kumar S3, Levy L1, Ferrigno O1, Tzivion G3, Atfi A4. Cell Rep. 2015 Feb 11. pii: S2211-1247(15)00049-2. doi: 10.1016/j.celrep.2015.01.024. [Epub ahead of print]
    • Functional characterization of a WWP1/Tiul1 tumor-derived mutant reveals a paradigm of its constitutive activation in human cancer. Courivaud T, Ferrand N, Elkhattouti A, Kumar S, Levy L, Ferrigno O, Atfi A, Prunier C. J Biol Chem. 2015 Jul 7. pii: jbc.M115.642314. [Epub ahead of print]
    • TGIF governs a feed-forward network that empowers Wnt signaling to drive mammary tumorigenesis. Zhang MZ, Ferrigno O, Wang Z, Ohnishi M, Prunier C, Levy L, Razzaque M, Horne WC, Romero D, Tzivion G, Colland F, Baron R, Atfi A. Cancer Cell. 2015 Apr 13;27(4):547-60. doi: 10.1016/j.ccell.2015.03.002.