# Receptor for hyaluronan-mediated motility isoform B (RHAMM B) in Pancreatic Cancer Metastasis

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $387,731

## Abstract

PROJECT SUMMARY
The 5-year survival is the lowest for cancers of the pancreas (<10%) among all cancers and the incidence of
pancreatic cancer continues to increase. The most common type of pancreatic cancer is pancreatic ductal
adenocarcinoma (PDAC), followed by pancreatic neuroendocrine tumor (PNET). Pancreatic cancer is usually
deadly due to metastatic dissemination and insufficient therapeutics. Factors driving metastasis of pancreatic
cancer remains largely unclear. There is an urgent need to understand the biology of pancreatic cancer
metastasis and develop new therapeutic strategies.
We were the first to report that Receptor for hyaluronan-mediated motility isoform B (RHAMMB), but not the full
length RHAMMA, promotes metastasis of PNET. We found that among different splice isoforms, RHAMMB was
significantly upregulated in human PDAC, and that higher RHAMMB predicted poorer survival of PDAC.
However, whether RHAMMB promotes PDAC metastasis is still unknown and will be determined in this
proposal work. Our preliminary data showed that RHAMMB overexpression induced RhoA signaling, migration,
3D spheroid invasion, and lipid droplet (LD) biogenesis in both PDAC and PNET cell lines, while RHAMMB
knockdown or pharmacological inhibition of RhoA signaling caused opposite effects. We hypothesis that
RHAMMB promotes pancreatic cancer metastasis through RhoA signaling/LD biogenesis and this RHAMMB
/RhoA/LD axis represents a novel therapeutic target.
To test this hypothesis, we will use multiple experimental systems, including cell lines, orthotopic tumor
xenograft, genetically engineered mouse models, and patient-derived xenografts. The findings will be cross-
examined. The success of this proposed study will establish the mechanisms by which RHAMMB promotes
pancreatic cancer metastasis and translated into new therapeutic approaches for treatment of this devastating
cancer.

## Key facts

- **NIH application ID:** 10522370
- **Project number:** 1R01CA266758-01A1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Yi-Chieh Nancy Du
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $387,731
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522370

## Citation

> US National Institutes of Health, RePORTER application 10522370, Receptor for hyaluronan-mediated motility isoform B (RHAMM B) in Pancreatic Cancer Metastasis (1R01CA266758-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10522370. Licensed CC0.

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