Isa M. Hussaini
- BS, Ahamadu Bello University Zaria, Nigeria
- MS, Chelsea College, University of London, UK
- PhD, King’s College, University of London, UK
- Associate Professor, Pathology
- Phone: 434-924-0110
- Email: firstname.lastname@example.org
The Roles of PKC-eta and LRP in Glioblastoma Invasive Growth
The prognosis for patients with malignant astroglial tumors is poor. The capacity of astrocytomas both to invade adjacent brain sites and to migrate into distant ones precludes curative surgical resection; and little progress has been made in designing adjuvant therapies that significantly affect long-term survival. In order to formulate more novel therapeutic strategies, it is essential to have a better understanding of how the invasive growth of these tumors is controlled.
The primary interest of the laboratory is the regulation of LRP (low density lipoprotein receptor-related protein) expression and function in astrocytic tumor cells. LRP is an endocytic receptor involved in the trafficking of a variety of protein/protein complexes that have pathophysiologic relevance in the central nervous system, including urokinase (uPA) and its receptor (uPAR), lipoprotein metabolites, and activated alpha2-macroglobulin. Changes in LRP expression may regulate the levels of modulators (uPA, uPAR and PAI-1) of migration/invasion around the microenvironment of astrocytic tumors.
The second project in my laboratory focuses on understanding differences in PKC-eta activation and expression between malignant vs. non-neoplastic astrocytes and on the role of PKC-eta in the control of cell proliferation and apoptosis. The regulation of cell proliferation and apoptosis in malignant astrocytic tumors is undoubtedly complex; however, we are investigating how PKC-eta regulation of these processes may be exploited to provide an experimental system in which proliferative or apoptotic phenotype may be selectively induced and studied. We are also extrapolating some of our results in cultured cells to glioblastoma animal models. We hypothesize that pharmacological regulation of PKC-eta, in combination with drugs targeting cellular migration, may present a new therapeutic paradigm for these aggressive brain tumors.
- Gong J, Zhao Y, Abdel-Fattah R, Amos S, Xiao A, Lopes M, Hussaini I, Laws E. Matrix metalloproteinase-9, a potential biological marker in invasive pituitary adenomas. Pituitary. 11(1): 37-48.
- Bush Z, Lopes M, Hussaini I, Jane J, Laws J, Vance M. Immunohistochemistry of COUP-TFI: an adjuvant diagnostic tool for the identification of corticotroph microadenomas. Pituitary. 13(1): 1-7.
- Abdel-Fattah R, Xiao A, Bomgardner D, Pease C, Lopes M, Hussaini I. Differential expression of HOX genes in neoplastic and non-neoplastic human astrocytes. J Pathol. 209(1): 15-24.
- Wang J, Wang N, Xie J, Walton S, McKown R, Raab R, Ma P, Beck S, Coffman G, Hussaini I, Laurie G. Restricted epithelial proliferation by lacritin via PKCalpha-dependent NFAT and mTOR pathways. J Cell Biol. 174(5): 689-700. PMCID: PMC1761701
- Hussaini I, Trotter C, Zhao Y, Abdel-Fattah R, Amos S, Xiao A, Agi C, Redpath G, Fang Z, Leung G, Lopes M, Laws J. Matrix metalloproteinase-9 is differentially expressed in nonfunctioning invasive and noninvasive pituitary adenomas and increases invasion in human pituitary adenoma cell line. Am J Pathol. 170(1): 356-65. PMCID: PMC1762693
- Martin P, Aeder S, Chrestensen C, Sturgill T, Hussaini I. Phorbol 12-myristate 13-acetate and serum synergize to promote rapamycin-insensitive cell proliferation via protein kinase C-eta. Oncogene. 26(3): 407-14.
- Uht R, Amos S, Martin P, Riggan A, Hussaini I. The protein kinase C-eta isoform induces proliferation in glioblastoma cell lines through an ERK/Elk-1 pathway. Oncogene. 26(20): 2885-93.
- Amos S, Mut M, diPierro C, Carpenter J, Xiao A, Kohutek Z, Redpath G, Zhao Y, Wang J, Shaffrey M, Hussaini I. Protein kinase C-alpha-mediated regulation of low-density lipoprotein receptor related protein and urokinase increases astrocytoma invasion. Cancer Res. 67(21): 10241-51. PMCID: PMC2386949
- Li Y, Guessous F, Kwon S, Kumar M, Ibidapo O, Fuller L, Johnson E, Lal B, Hussaini I, Bao Y, Laterra J, Schiff D, Abounader R. PTEN has tumor-promoting properties in the setting of gain-of-function p53 mutations. Cancer Res. 2008;68(6): 1723-31. PMCID: NIHMS135586
- Zhao Y, Lyons J, Xiao A, Templeton D, Sang Q, Brew K, Hussaini I. Urokinase directly activates matrix metalloproteinases-9: a potential role in glioblastoma invasion. Biochem Biophys Res Commun. 2008;369(4): 1215-20. PMCID: PMC2562868
- Zhao Y, Xiao A, Dipierro C, Abdel-Fattah R, Amos S, Redpath G, Carpenter J, Pieper R, Hussaini I. H-Ras increases urokinase expression and cell invasion in genetically modified human astrocytes through Ras/Raf/MEK signaling pathway. Glia. 2008;56(8): 917-24. PMCID: PMC2408768
- Kohutek Z, diPierro C, Redpath G, Hussaini I. ADAM-10-mediated N-cadherin cleavage is protein kinase C-alpha dependent and promotes glioblastoma cell migration. J Neurosci. 29(14): 4605-15. PMCID: NIHMS107874
- Amos S, Redpath G, Dipierro C, Carpenter J, Hussaini I. Epidermal growth factor receptor-mediated regulation of urokinase plasminogen activator expression and glioblastoma invasion via C-SRC/MAPK/AP-1 signaling pathways. Journal of neuropathology and experimental neurology. 2010;69(6): 582-92. PMID: 20467333 | PMCID: NIHMS304365
- Zhao Y, Xiao A, diPierro C, Carpenter J, Abdel-Fattah R, Redpath G, Lopes M, Hussaini I. An extensive invasive intracranial human glioblastoma xenograft model: role of high level matrix metalloproteinase 9. The American journal of pathology. 2010;176(6): 3032-49. PMID: 20413683 | PMCID: PMC2877863
- Zhao Y, Xiao A, diPierro C, Carpenter J, Abdel-Fattah R, Redpath G, Lopes M, Hussaini I. An extensive invasive intracranial human glioblastoma xenograft model: role of high level matrix metalloproteinase 9. Am J Pathol. 176(6): 3032-49. PMCID: PMC2877863
- Amos S, Redpath G, Dipierro C, Carpenter J, Hussaini I. Epidermal growth factor receptor-mediated regulation of urokinase plasminogen activator expression and glioblastoma invasion via C-SRC/MAPK/AP-1 signaling pathways. J Neuropathol Exp Neurol. 69(6): 582-92.
- Merk B, Owens J, Lopes M, Silva C, Hussaini I. STAT6 expression in glioblastoma promotes invasive growth. BMC cancer. 2011;11 184. PMID: 21595984 | PMCID: PMC3118945
- Sherman J, Redpath G, Redick J, Purow B, Laws E, Jane J, Shaffrey M, Hussaini I. A novel fixative for immunofluorescence staining of CD133-positive glioblastoma stem cells. Journal of neuroscience methods. 2011;198(1): 99-102. PMID: 21402102 | PMCID: PMC3126626
- Sherman J, Redpath G, Redick J, Purow B, Laws E, Jane J, Shaffrey M, Hussaini I. A novel fixative for immunofluorescence staining of CD133-positive glioblastoma stem cells. J Neurosci Methods. 198(1): 99-102. PMCID: PMC3126626
- Merk B, Owens J, Lopes M, Silva C, Hussaini I. STAT6 expression in glioblastoma promotes invasive growth. BMC Cancer. 11 184.0. PMCID: PMC3118945