# Pancreatic Cancer Metastasis

> **NIH NIH P01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2020 · $1,644,289

## Abstract

ABSTRACT
The overall goal of this P01 proposal is to define the mechanistic role of MUC16 in facilitating pancreatic
cancer (PC) metastasis. It is well known pancreatic cancer is one of the lethal cancers and also a diffuse
metastatic disease with approximately 45% to 55% of patients diagnosed after the cancer has spread. The
molecular mechanisms of metastasis are poorly understood. In cancer cells depolarized mucin expression
contributes to altered cell-cell adhesion, aberrant potentiation of growth factor receptor signaling, epithelial-to-
mesenchymal transition, and drug resistance. In our recent study we have observed that MUC16/CA125 is a
membrane bound mucin, and we have observed its aberrant overexpression during PC progression while no
expression was observed in the normal pancreas. Similarly our collaborative study demonstrates that the
prognosis of patients with MUC16 cytoplasmic expression was significantly poorer in pancreatic cancer
patients. Based on these studies and our preliminary results our general hypothesis for the program project is
that MUC16-Cter-mediated signaling, biological effects resulting from mutations of MUC16, and MUC16-
induced metabolic reprograming contribute to PC metastasis. To test this hypothesis we are proposing three
highly integrated projects investigating the mechanisms by which a multi-domain, muti-functional mucin
MUC16 promotes metastasis. First project will focus on the role and mechanism(s) of MUC16 and its C-
terminal domain in the metastatic progression of PC. Project 1 will be led by Batra, who has 26 years of
experience in the field of pancreatic cancer and mucin biology. Second project will explore the roles of
mutated forms of membrane bound and circulating MUC16 and its glycosylation in PC metastasis. This project
will be led by Hollingsworth, who has 27 years of experience in the field of pancreatic cancer and mucin
biology. Third project will focus on MUC16-mediated metabolic reprograming that induces PC metastasis.
This project will be led by Singh, who has 14 years of experience in the field of pancreatic cancer biology. The
projects are supported by two scientific cores to facilitate animal studies (Core B), evaluate therapeutic
strategies and support clinical and animal tissue collection and analysis (Core C). Additionally, an
Administrative and Bioinformatics Core (A) is proposed to integrate the different projects, cores and
investigators, provide a coordinated management structure and bioinformatics and statistical data analysis.
Overall this P01 program builds on the ongoing strengths in pancreatic cancer research that exist at UNMC
and has resulted from a long and productive history of collaboration of participating investigators. We hope to
define novel mechanisms of MUC16 mediated PC metastasis which will pave a way for better management of
this lethal disease.

## Key facts

- **NIH application ID:** 9940705
- **Project number:** 5P01CA217798-03
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Surinder K. Batra
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,644,289
- **Award type:** 5
- **Project period:** 2018-06-08 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9940705

## Citation

> US National Institutes of Health, RePORTER application 9940705, Pancreatic Cancer Metastasis (5P01CA217798-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9940705. Licensed CC0.

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