# Project 3-Cancer cell interaction with oncogenic type 1 collagen in PDAC

> **NIH NIH P01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2024 · $529,109

## Abstract

Project 3 -­ Abstract/Summary 
The desmoplastic stroma, consisting of fibroblasts, extracellular matrix (ECM) and immune cells, is a defining 
feature of human pancreatic ductal adenocarcinoma (PDAC), however its precise contribution to cancer 
progression is still evolving. Type I collagen (Col1), a dominant component of PDAC desmoplasia, is uniquely 
regulated in PDAC. Our preliminary studies uncovered that cancer cells produce a novel Col1 variant consisting 
of alpha 1 chain (Col1a1) homotrimers. Genetic deletion of the oncogenic Col1 in cancer cells extends the overall 
lifespan of PDAC genetically engineered mice (GEMs). Oncogenic Kras (Kras*), a central driver for PDAC, plays 
a key role in determining the host response, including tumor immunity and metabolic adaptation. We discovered 
that Kras* drives cancer cells’ production of oncogenic Col1 via epigenetic silencing of Col1a2. In contrast with 
the classical Col1 heterotrimer produced by fibroblasts, oncogenic Col1 uniquely promotes PDAC initiation and 
progression by influencing tumor metabolism and immunity. Col1 homotrimers bind to a?3b?1 integrin on PDAC 
cancer cells, a collagen receptor distinctly upregulated in mouse and human PDAC. This induces a sustained 
activation of FAK, Akt and Erk1/2 when compared with Col1 heterotrimers, promoting cancer cells growth and 
survival. Oncogenic Col1 also suppresses intratumoral T cells, and oncogenic Col1 deletion synergizes with anti-­
PD-­1 immune checkpoint blockade to suppress tumor growth and increase overall survival of PDAC GEMs. 
Cancer cell-­directed oncogenic Col1 homotrimer signaling also enhances glycolysis and mTOR signaling, 
supporting the metabolic reprogramming driven by Kras*. In Project 3, in close collaboration with Projects 1 and 
2, we will define the role and regulation of Kras*-­induced oncogenic Col1 signaling in impacting tumor immunity 
and metabolism. The proposed aims investigate Col1 homotrimers-­ a?3b?1 integrin targeting, immunotherapy, and 
anti-­metabolism strategies, as an informed combination treatment modality. Our preliminary data support the 
feasibility and significance of this novel approach, and exploit a new vulnerability in PDAC signaling, with a 
translational potential to inform new therapies for PDAC.

## Key facts

- **NIH application ID:** 10829380
- **Project number:** 5P01CA117969-19
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** RAGHU KALLURI
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $529,109
- **Award type:** 5
- **Project period:** 2005-12-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829380

## Citation

> US National Institutes of Health, RePORTER application 10829380, Project 3-Cancer cell interaction with oncogenic type 1 collagen in PDAC (5P01CA117969-19). Retrieved via AI Analytics 2026-06-25 from https://api.ai-analytics.org/grant/nih/10829380. Licensed CC0.

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