Tumor cells resist the apoptotic stimuli associated with invasion and metastasis by activating survival signals that suppress apoptosis. Focal adhesion kinase (FAK), a tyrosine is overexpressed in variety of human tumors, mediates one these signals. Attenuation FAK expression tumor results apoptosis mediated caspase 8- FADD-dependent pathways, suggesting death receptor pathways are involved process. Here, we report functional link between receptors. We have demonstrated binds to domain...

Pancreatic cancer is a lethal disease accounting for the fourth leading cause of death in USA. Focal adhesion kinase (FAK) and insulin-like growth factor-I receptor (IGF-1R) are tyrosine kinases that activate common pathways, to increased proliferation cell survival. Sparse information available regarding their contribution malignant behavior pancreatic cancer. We analyzed relationship between FAK IGF-1R human cells, determined which downstream signaling pathways altered following inhibition...

FAK is a tyrosine kinase that functions as key orchestrator of signals leading to invasion and metastasis. Since interacts directly with number critical proteins involved in survival signaling tumor cells, we hypothesized targeting protein-protein interface druglike small molecules was feasible strategy for inhibiting growth. In this study, targeted the between VEGFR-3 identified compound C4 (chloropyramine hydrochloride) drug capable (1) biochemical function FAK, (2) proliferation diverse...

Abstract Focal adhesion kinase (FAK) and vascular endothelial growth factor receptor-3 (VEGFR-3) are protein tyrosine kinases that overexpressed in human cancer play an important role survival signaling. In addition to its involvement with cell survival, VEGFR-3 is a primary lymphatic angiogenesis. Because FAK function regulated by COOH terminus (FAK-CD), we used FAK-CD as target identify binding partners. We isolated peptide from phage library bound FAK-CD, specifically the focal targeting...

N-MYC is a transcription factor that plays an important role in cellular survival neuroblastoma, and amplification of the oncogene primary adverse prognostic indicator for neuroblastoma. Focal adhesion kinase (FAK) has been shown to be overexpressed many types human cancers. In this study, we investigated regulation FAK expression We first found correlation between Real time quantitative PCR demonstrated increase mRNA abundance N-MYC-amplified IMR-32 compared with nonamplified SK-N-AS...

Abstract The NF1 gene that is altered in patients with type 1 neurofibromatosis (NF1) encodes a neurofibromin protein functions as tumor suppressor. In this report, we show for the first time physical interaction between and focal adhesion kinase (FAK), localizes at adhesions. We associates N‐terminal domain of FAK, C‐terminal directly interacts FAK. Confocal microscopy demonstrates colocalization FAK cytoplasm, perinuclear nuclear regions inside cells. Nf1 +/+ MEF cells expressed less cell...

Abstract Purpose: The focal adhesion kinase (FAK) is a nonreceptor protein tyrosine important in signaling between cells and their extracellular matrix. Studies have shown that FAK expression up-regulated several human tumors related to tumor progression. We recently found an increase p125FAK neuroblastoma lines wished determine its specimens evaluate for possible correlation known prognostic factors neuroblastoma. hypothesized would be advanced neuroblastomas. Experimental Design: Using...

FAK (focal adhesion kinase) and IGF-1R (insulin-like growth factor receptor-1) directly interact with each other thereby activate crucial signaling pathways that benefit cancer cells. Inhibition of function has been shown to significantly decrease cell proliferation increase sensitivity chemotherapy radiation treatment. As a novel approach in human melanoma, we evaluated the effect small-molecule compound disrupts protein interaction IGF-1R. Previously, using virtual screening functional...

Vascular endothelial growth factor receptor-3 is a receptor tyrosine kinase that overexpressed in some human carcinomas, but its role tumorigenesis has not been fully elucidated. We examined VEGFR-3 expression normal, nonneoplastic and early stage malignant breast tissues have shown upregulation cancer preceded tumor cell invasion, suggesting may function as survival signal. characterized the biological effects of overexpression cells based on two approaches: Gain by overexpressing MCF-7...

Abstract Neuroblastoma is the most common extracranial solid tumor of childhood. Focal adhesion kinase (FAK) an intracellular that overexpressed in a number human tumors including neuroblastoma, and regulates both cellular survival. We have studied effects FAK inhibition upon neuroblastoma using adenovirus‐containing FAK‐CD (AdFAK‐CD). Utilizing isogenic MYCN+/MYCN− cell line, we found MYCN+ cells are more sensitive to with AdFAK‐CD than their MYCN negative counterparts. In addition, shown...

Even with successful surgical resection and perioperative chemotherapy radiation, pancreatic ductal adenocarcinoma (PDA) has a high incidence of recurrence. Tumor cell survival depends on activation signaling pathways that suppress the apoptotic stimuli invasion metastasis. Focal adhesion kinase (FAK) is critical molecule been implicated in tumor survival, We have previously shown FAK vascular endothelial growth factor receptor 3 (VEGFR-3) are overexpressed cancer cells physically interact...

It is known that p53 alterations are commonly found in tumour cells. Another marker of tumorigenesis FAK (focal adhesion kinase), a non-receptor kinase overexpressed many types tumours. Previously we determined the N-terminal domain physically interacted with p53. In present study, using phage display, sitedirected mutagenesis, pulldown and immunoprecipitation assays localized site binding to 7-amino-acid region(amino acids 65-71) proline-rich human Mutation reversed suppressive effect on...

Deregulation of insulin-like growth factor-1 receptor (IGF-1R) and focal adhesion kinase (FAK) signaling pathways plays an important role in cancer cell proliferation metastasis. In pancreatic cells, the crosstalk compensatory mechanisms between these two reduce efficacy treatments that target only one pathways. Ablation IGF-1R by siRNA showed minimal effects on survival cells. An increased activity FAK pathway was seen cells after knockdown. Further inhibition using Y15 significantly...

Neuroblastoma is one of the most devastating pediatric solid tumors and unresponsive to many interventions. TAE226 a novel small molecule FAK inhibitor. We investigated effects on neuroblastoma cells in vitro.Human cell lines were treated with varying concentrations TAE226. Following treatment, viability, cycle, apoptosis evaluated.Treatment human resulted concentration dependent decrease phosphorylation, cellular cycle arrest, an increase apoptosis.Targeting provides potential therapeutic...

Abstract The HeT-A element is a transposable with an apparent role in the structure of telomeres Drosophila melanogaster chromosomes. transposition earliest event detected healing broken ends; also found on unbroken Sequences homology to are never euchromatic regions; however, clusters HeT-A-related sequences occur nontelomeric regions heterochromatic Y chromosome. Analysis two these Y-associated shows them be significantly different from telomeric elements, although shared sequence have...

Pancreatic cancer is one of the most lethal diseases with no effective treatment. Previously, we have shown that FAK overexpressed in pancreatic and plays a key role cell survival proliferation. has been to interact growth factor receptors including cMET IGF-1R. As novel therapeutic approach, targeted protein interaction block tumor growth, alter signaling pathways sensitize cells chemotherapy. We selected small molecule compound (INT2-31) decreases phosphorylation AKT via disrupting Our...

Abstract Neuroblastoma is the most common extracranial solid tumor of childhood and responsible for over 15% pediatric cancer deaths. Focal adhesion kinase (FAK) a nonreceptor tyrosine that important in many facets development progression. Vascular endothelial growth factor receptor‐3 (VEGFR‐3), another kinase, has also been found to be human tumors including neuroblastoma. Recent reports have FAK VEGFR‐3 interact, we previously shown both these kinases interact We hypothesized interruption...

Melanoma has the highest mortality rate of all skin cancers and a major cause treatment failure is drug resistance. Tumors heterogeneity requires novel therapeutic strategies new drugs targeting multiple pathways. One approaches scaffolding function tumor related proteins such as focal adhesion kinase (FAK). FAK overexpressed in most solid tumors involved protein-protein interactions critical for cell survival, neovascularization, progression metastasis. In this study, we investigated...