This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Pancreatic cancer is the fourth most frequent cause of cancer-related death in the U.S., and only about 5% of patients with this disease survive. Improved comprehension of how pancreatic tumors grow and metastasize is necessary in order for better therapies to be developed. In some systems, principally the nervous system, amyloid precursor protein (APP) and amyloid precursor-like-protein 2 (APLP2) have been associated with cellular growth and migration. Recent studies have shown over-expression of APP and APLP2 in human cancer, including pancreatic cancer, and in some cancers higher APP expression has been shown to correlate with a worse survival rate. APP secreted by prostate and pancreatic cancer cell lines increases proliferation by binding to an unidentified cell surface receptor, and both APP and APLP2 contribute to adhesion and motility in several cell types. There is evidence that APP and APLP2 have novel roles in pancreatic cancer, but the mechanisms for how they contribute to this disease are not known. In this project, our overall objective is to gain understanding of mechanisms underlying pancreatic cancer growth and spread. Our central hypothesis is that APP and APLP2 stimulate the proliferation and metastasis of pancreatic cancer cells. To accomplish this objective, our Aims are, first, to ascertain mechanisms mediated by APP and APLP2 that facilitate pancreatic cancer cell growth. Our working hypothesis for this aim is that secreted APLP2 and APP trigger the proliferation of pancreatic cancer cells via a NF-?B pathway.
The second aim i s to determine mechanisms mediated by APP and APLP2 that increase the spread of pancreatic cancer cells. The working hypothesis that will be tested in this aim is that transmembrane APP and APLP2 are key regulators of the adhesion and dissemination of pancreatic cancer cells. Our results from these studies will provide a novel perspective on the regulation of cellular growth and motility, with relevance to normal and cancer cells and particularly to pancreatic cancer cells. Furthermore, results from this study are expected to support the use of novel treatments for pancreatic cancer that target APP and APLP2.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR018759-09
Application #
8360444
Study Section
Special Emphasis Panel (ZRR1-RI-6 (01))
Project Start
2011-07-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
9
Fiscal Year
2011
Total Cost
$14,237
Indirect Cost
Name
University of Nebraska Medical Center
Department
Dentistry
Type
Schools of Dentistry
DUNS #
168559177
City
Omaha
State
NE
Country
United States
Zip Code
68198
Rector, Jeff; Kapil, Sasha; Treude, Kelly J et al. (2017) S4S8-RPA phosphorylation as an indicator of cancer progression in oral squamous cell carcinomas. Oncotarget 8:9243-9250
Glanzer, Jason G; Endres, Jennifer L; Byrne, Brendan M et al. (2016) Identification of inhibitors for single-stranded DNA-binding proteins in eubacteria. J Antimicrob Chemother 71:3432-3440
Glanzer, Jason G; Byrne, Brendan M; McCoy, Aaron M et al. (2016) In silico and in vitro methods to identify ebola virus VP35-dsRNA inhibitors. Bioorg Med Chem 24:5388-5392
Xie, Shuwei; Bahl, Kriti; Reinecke, James B et al. (2016) The endocytic recycling compartment maintains cargo segregation acquired upon exit from the sorting endosome. Mol Biol Cell 27:108-26
Ghospurkar, Padmaja L; Wilson, Timothy M; Liu, Shengqin et al. (2015) Phosphorylation and cellular function of the human Rpa2 N-terminus in the budding yeast Saccharomyces cerevisiae. Exp Cell Res 331:183-99
McAtee, Caitlin O; Berkebile, Abigail R; Elowsky, Christian G et al. (2015) Hyaluronidase Hyal1 Increases Tumor Cell Proliferation and Motility through Accelerated Vesicle Trafficking. J Biol Chem 290:13144-56
Moore, Tyler C; Vogel, Alexander J; Petro, Thomas M et al. (2015) IRF3 deficiency impacts granzyme B expression and maintenance of memory T cell function in response to viral infection. Microbes Infect 17:426-39
Simpson, Melanie A; Heldin, Paraskevi (2014) Hyaluronan signaling and turnover. Preface. Adv Cancer Res 123:xv-xvi
McAtee, Caitlin O; Barycki, Joseph J; Simpson, Melanie A (2014) Emerging roles for hyaluronidase in cancer metastasis and therapy. Adv Cancer Res 123:1-34
Liu, Xiang; Yi, Chunhui; Wen, Yunfei et al. (2014) Interactions between MUC1 and p120 catenin regulate dynamic features of cell adhesion, motility, and metastasis. Cancer Res 74:1609-20

Showing the most recent 10 out of 106 publications