We propose to study lymphatic invasion and metastasis to lymph nodes, an early feature of metastasis of all adenocarcinomas. This proposal is to study the process of lymphatic invasion and metastasis in pancreatic cancer by undertaking both hypothesis-driven and hypothesis-generating specific aims.
The first aim, which is hypothesis driven, seeks to further invesfigate the role of Sonic Hedgehog (SHH) in tumor lymphangiogenesis and metastasis to lymph nodes. SHH is expressed in premalignant and malignant ductal epithelial cells of the pancreas, implicafing this morphogenic signaling protein in the inifiafion and progression of pancreafic cancer.
Aim 1 will build upon our recent published work [1] and other recent unpublished findings. We were the first to show that SHH contributes significantly to lymphangiogenesis by invesfigating the nature of paracrine signaling between pancreatic tumor cells producing SHH and lymphatic endothelial cells that are responding to SHH in the context of the emerging desmoplasfic reaction in pancreatic cancer.

Agency
National Institute of Health (NIH)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA163120-04
Application #
8711370
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Nebraska Medical Center
Department
Type
DUNS #
City
Omaha
State
NE
Country
United States
Zip Code
68198
Hanson, Ryan L; Brown, Roger B; Steele, Maria M et al. (2016) Identification of FRA-1 as a novel player in pancreatic cancer in cooperation with a MUC1: ERK signaling axis. Oncotarget 7:39996-40011
Pai, Priya; Rachagani, Satyanarayana; Dhawan, Punita et al. (2016) MUC4 is negatively regulated through the Wnt/β-catenin pathway via the Notch effector Hath1 in colorectal cancer. Genes Cancer 7:154-68
Muniyan, Sakthivel; Haridas, Dhanya; Chugh, Seema et al. (2016) MUC16 contributes to the metastasis of pancreatic ductal adenocarcinoma through focal adhesion mediated signaling mechanism. Genes Cancer 7:110-24
Huang, Huocong; Svoboda, Robert A; Lazenby, Audrey J et al. (2016) Up-regulation of N-cadherin by Collagen I-activated Discoidin Domain Receptor 1 in Pancreatic Cancer Requires the Adaptor Molecule Shc1. J Biol Chem 291:23208-23223
Clausen, Thomas Mandel; Pereira, Marina Ayres; Al Nakouzi, Nader et al. (2016) Oncofetal Chondroitin Sulfate Glycosaminoglycans Are Key Players in Integrin Signaling and Tumor Cell Motility. Mol Cancer Res 14:1288-1299
Joshi, Suhasini; Cruz, Eric; Rachagani, Satyanarayana et al. (2016) Bile acids-mediated overexpression of MUC4 via FAK-dependent c-Jun activation in pancreatic cancer. Mol Oncol 10:1063-77
Pai, Priya; Rachagani, Satyanarayana; Dhawan, Punita et al. (2016) Mucins and Wnt/β-catenin signaling in gastrointestinal cancers: an unholy nexus. Carcinogenesis 37:223-32
Gunda, Venugopal; Yu, Fang; Singh, Pankaj K (2016) Validation of Metabolic Alterations in Microscale Cell Culture Lysates Using Hydrophilic Interaction Liquid Chromatography (HILIC)-Tandem Mass Spectrometry-Based Metabolomics. PLoS One 11:e0154416
Vaz, Arokia Priyanka; Deb, Shonali; Rachagani, Satyanarayana et al. (2016) Overexpression of PD2 leads to increased tumorigenicity and metastasis in pancreatic ductal adenocarcinoma. Oncotarget 7:3317-31
Hein, Ashley L; Seshacharyulu, Parthasarathy; Rachagani, Satyanarayana et al. (2016) PR55α Subunit of Protein Phosphatase 2A Supports the Tumorigenic and Metastatic Potential of Pancreatic Cancer Cells by Sustaining Hyperactive Oncogenic Signaling. Cancer Res 76:2243-53

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