# Adipose tissue-colorectal tumor cross-talk: new targets for breaking the obesity-cancer link

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $677,102

## Abstract

SUMMARY
The pandemic rise of obesity worldwide is alarming, with the highest increases occurring in the United States.
Obesity is a major risk factor for many cancer types, including colon cancer (CC). To date, the biologic
mechanisms underlying this relationship, specifically the potential signaling between dysregulated adipose
tissue and adjacent tumor, are incompletely understood. Given the rising rates of obesity and the challenges
for many people to lose excess adipose tissue, an integrated, multilevel approach to efficiently identify
crosstalk and validate key molecular targets is needed to develop effective mechanism-based strategies for
prevention and control of obesity-driven CC. We hypothesize that the metabolic and inflammatory
perturbations induced by obesity increase CC risk through altered signaling between adipocytes and colon
epithelial/tumor cells, and that inhibition of this crosstalk will disrupt the obesity-CC link.
 We will test this hypothesis through the integration of: 1) a unique, prospective, multicenter epidemiologic
cohort of normoweight to obese CC patients, from whom paired serum, tumor, and tumor-adjacent adipose
tissue samples will be used to discover and validate lead targets; and 2) complementary in vivo models of lean
and diet-induced obese mice with CC, together with in vitro/in vivo organoid models in which potential targets
underlying the effects of obesity on CC will be tested mechanistically. This unique transdisciplinary approach
utilizes innovative clinical/epidemiological and preclinical studies of biochemical, transcriptomic, and
metabolomics analyses in rigorous study designs to identify and validate new targets for disrupting the
reciprocal crosstalk between adipocytes and colonic epithelial cells. We propose three synergistic aims: 1a) to
discover and validate targets underlying the adipose tissue-CC link, using 400 CC patients; b) to identify and
validate metabolic and transcriptomic signatures of adipocyte-colonocyte crosstalk; 2) to characterize the
adipocyte-colonocyte crosstalk underlying the obesity-CC link, using two rigorous mouse models of CC; 3) to
determine the causal role of candidate epithelial target genes in obesity-associated CC progression using
murine in vitro and in vivo organoid CC models.
 This paradigm-shifting transdisciplinary collaboration builds on extensive preliminary data and generates
maximum synergy through complementary human and murine studies, using identical state-of-the-art
biomarker panels and platforms across clinical and preclinical studies. We anticipate that findings from these
proposed studies will address the clinical challenges associated with obesity and CC by establishing causal
links of the most promising targets for intercepting and disrupting adipocyte-epithelial cell crosstalk.

## Key facts

- **NIH application ID:** 10229282
- **Project number:** 1R01CA254108-01A1
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Stephen D Hursting
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $677,102
- **Award type:** 1
- **Project period:** 2021-09-23 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229282

## Citation

> US National Institutes of Health, RePORTER application 10229282, Adipose tissue-colorectal tumor cross-talk: new targets for breaking the obesity-cancer link (1R01CA254108-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10229282. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*