This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hecker, T. P. Articles by Gladson, C. L. Search for Related Content PubMed PubMed Citation Articles by Hecker, T. P. Articles by Gladson, C. L.

Focal Adhesion Kinase Enhances Signaling through the Shc/Extracellular Signal-regulated Kinase Pathway in Anaplastic Astrocytoma Tumor Biopsy Samples¹

Department of Pathology, Division of Neuropathology [T. P. H., J. R. G., J. S., C. L. G.], The Medical Scientist Training Program [T. P. H.], and the Department of Surgery, Division of Neurosurgery [G. Y. G.], The University of Alabama at Birmingham, Birmingham, Alabama 35294

Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that on activation generates signals that can modulate crucial cell functions, including cell proliferation, migration, and survival. In vitro, overexpression of FAK has been shown to promote cell proliferation by signaling through the Ras/mitogen-activated protein kinase cascade in several cell types. We have shown previously that overexpression of exogenous FAK lacking alternative splicing in malignant astrocytoma clones injected intracerebrally into SCID mouse brains promotes tumor cell proliferation. Here, we show that in anaplastic astrocytoma biopsy samples, FAK is expressed as an unspliced variant and migrates with a faster mobility similar to that observed in embryonic brain. Compared with nonneoplastic adult brain biopsies, the levels of FAK protein are elevated as are its levels of activation as assessed by autophosphorylation and overall tyrosine phosphorylation. The activity of Src kinase in these tumors is also elevated, as well as the activity of Src kinase associated with FAK; the latter may result in enhanced Src kinase phosphorylation of FAK. Phosphorylated Shc is associated with FAK in the anaplastic astrocytoma biopsy samples and in astrocytoma cells overexpressing FAK in vitro but not in nonneoplastic brain biopsy samples. Elevated extracellular signal-regulated kinase-2 activation and elevated expression of cyclins D and E are also found in anaplastic astrocytoma biopsy samples. These data provide evidence that the increased FAK activity in these tumors contributes to phosphorylation of Shc and likely to the promotion of Ras activity, extracellular signal-regulated kinase-2 activation, and cell proliferation in vivo.

This article has been cited by other articles:

				J. Halder, A. A. Kamat, C. N. Landen Jr., L. Y. Han, S. K. Lutgendorf, Y. G. Lin, W. M. Merritt, N. B. Jennings, A. Chavez-Reyes, R. L. Coleman, et al. Focal Adhesion Kinase Targeting Using In vivo Short Interfering RNA Delivery in Neutral Liposomes for Ovarian Carcinoma Therapy. Clin. Cancer Res., August 15, 2006; 12(16): 4916 - 4924. [Abstract] [Full Text] [PDF]

				P. Bryant, Q. Zheng, and K. Pumiglia Focal Adhesion Kinase Controls Cellular Levels of p27/Kip1 and p21/Cip1 through Skp2-Dependent and -Independent Mechanisms. Mol. Cell. Biol., June 1, 2006; 26(11): 4201 - 4213. [Abstract] [Full Text] [PDF]

				H. Park, I. Han, H. J. Kwon, and E.-S. Oh Focal Adhesion Kinase Regulates Syndecan-2-Mediated Tumorigenic Activity of HT1080 Fibrosarcoma Cells Cancer Res., November 1, 2005; 65(21): 9899 - 9905. [Abstract] [Full Text] [PDF]

				M. R. Stettner, W. Wang, L. B. Nabors, S. Bharara, D. C. Flynn, J. R. Grammer, G. Y. Gillespie, and C. L. Gladson Lyn Kinase Activity Is the Predominant Cellular Src Kinase Activity in Glioblastoma Tumor Cells Cancer Res., July 1, 2005; 65(13): 5535 - 5543. [Abstract] [Full Text] [PDF]

				Q. Ding, J. R. Grammer, M. A. Nelson, J.-L. Guan, J. E. Stewart Jr., and C. L. Gladson p27Kip1 and Cyclin D1 Are Necessary for Focal Adhesion Kinase Regulation of Cell Cycle Progression in Glioblastoma Cells Propagated in Vitro and in Vivo in the Scid Mouse Brain J. Biol. Chem., February 25, 2005; 280(8): 6802 - 6815. [Abstract] [Full Text] [PDF]

				Y. Lim, I. Han, J. Jeon, H. Park, Y.-Y. Bahk, and E.-S. Oh Phosphorylation of Focal Adhesion Kinase at Tyrosine 861 Is Crucial for Ras Transformation of Fibroblasts J. Biol. Chem., July 9, 2004; 279(28): 29060 - 29065. [Abstract] [Full Text] [PDF]

				S. Xi, Q. Zhang, K. F. Dyer, E. C. Lerner, T. E. Smithgall, W. E. Gooding, J. Kamens, and J. R. Grandis Src Kinases Mediate STAT Growth Pathways in Squamous Cell Carcinoma of the Head and Neck J. Biol. Chem., August 22, 2003; 278(34): 31574 - 31583. [Abstract] [Full Text] [PDF]

				H. Haskell, M. Natarajan, T. P. Hecker, Q. Ding, J. Stewart Jr., J. R. Grammer, and C. L. Gladson Focal Adhesion Kinase Is Expressed in the Angiogenic Blood Vessels of Malignant Astrocytic Tumors in Vivo and Promotes Capillary Tube Formation of Brain Microvascular Endothelial Cells Clin. Cancer Res., June 1, 2003; 9(6): 2157 - 2165. [Abstract] [Full Text] [PDF]