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
    E-mail: aatfi@umc.edu

    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, thereby promoting TGF-β signaling. Since the PHRF1 gene localizes to the 11p15.5 locus, which is frequently deleted in human tumors, we are interested in investigating whether PHRF1 could function as a tumor suppressor, focusing on pancreatic cancer and osteosarcoma. 
    • TGIF and pancreatic ductal adenocarcinoma: pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplasms. We found that genetic deletion of TGIF accelerated the development and progression of PDAC driven by Kras.G12D, an oncogenic form of Kras found in more than 90% of human PDAC. In addition, we found that TGIF function as transcriptional repressor of the transcription factor Twist1, which plays an important role in PDAC metastasis. Another ongoing project is to investigate whether TGIF promotes PDAC metastasis in vivo through its ability to repress Twist1 transcription.
    • 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 formation and osteosarcoma progression.

     

    Selected publications

     

    • TGIF Governs a feed-forward Network that empowers Wnt signaling to drive mammary tumorigenesis. Zhang, M.Z., Ferrigno, O., Wang, Z., Ohnishi, M., Prunier, C., Levy, L., Razzaque, M., Horne, W.C., Damian, R., Tzivion, G., Colland, F., Baron, R., and Atfi A. Cancer Cell, 27: 547-560, 2015.
    • Inactivation of the PHRF1 Tumor Suppressor by PML-RAR Drives Acute Promyelocytic Leukemia Pathogenesis. Prunier, C., Zhang, M.Z., Kumar, S., Levy, L., Ferrigno, O., Tzivion, G., and Atfi, A. Cell Reports, 10: 883-890, 2015.
    • Identification of PHRF1 as a Tumor Suppressor that Promotes the TGF-Cytostatic Program Through Selective release of TGIF-Driven PML Inactivation. Ettahar, A., Ferrigno, O., Zhang, M.Z., Ohnishi, M., Ferrand, N., Prunier, P., Levy, L., Bourgeade, M.F., Bieche, I., Romero, D., Colland, F., and Atfi, A. Cell Reports,4: 530-541, 2013.
    • PTH battles TGF-b in bone.  Atfi, A. and Baron R. 2010. Nature Cell Biology, 12: 205-  207.
    • p53 brings a new twist to the Smad signaling network. Atfi, A. and Barron, R. Science Signaling, July 1, p33, 2008.
    • A model of Partnership co-opted by the homeodomain protein TGIF and the ubiquitin ligase for effective execution of TNF-cytotoxicity. Demange, C., Ferrand, N., Prunier, C., Bourgeade, M.F., and Atfi, A. Molecular Cell, 36: 1073-1085, 2009.