# Mechanisms for environmental microplastics-enhanced colorectal tumor progression

> **NIH NIH R01** · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · 2024 · $453,688

## Abstract

Project Summary
In response to the Notice of Special Interest (NOSI) NOT-ES-23-002, our research addresses the urgent
concern of escalating plastic pollution. Despite numerous reports indicating the ubiquitous presence of plastics
in the environment and growing global concern for ecosystems and human health, plastic production and use
continue to grow unabatedly. Humans are exposed to plastic particles mainly through ingestion of
contaminated food or water, through inhalation, or through skin contact. Humans consume up to 5g (weight of
a credit card) microplastics weekly, and colonic epithelial cells will face the brunt of this toxic exposure. Recent
studies provide evidence for the accumulation of microplastics in multiple human organs including the colon.
Toxic exposure to microplastics has been linked to the disruption of colonic epithelial cell structure and
function. Moreover, studies in different preclinical models including mice indicate that microplastics exposure
leads to various adverse intestinal effects including inflammation, barrier dysfunction, and microbial imbalance.
Long-standing intestinal inflammation and oxidative stress increase the risk of colorectal cancer (CRC)
development. However, to date, there have been no studies investigating the influence of microplastics on
colon tumor growth and metastasis in vivo. Thus, investigation into the potential association between the
environmental microplastics exposure and the risk of CRC is merited. Our objective is to unveil the molecular
mechanisms linking microplastics exposure to CRC. We hypothesize that microplastics trigger PIEZO1-
dependent oxidative stress and hypoxia inducible factor (HIF)-3α signaling, promoting CRC progression. Our
hypothesis is based on our data showing that different microplastics consistently and dramatically promote
oxidative stress in a mechanosensing ion channel PIEZO1 dependent manner. Moreover, microplastics
activate HIF-3α signaling, which drives growth, migration, and metastasis of colon tumors in preclinical models.
The proposal highlights the unique PIEZO1 trigger (Aim 1) and the immediate downstream HIF-3α signaling
(Aim 2) of oxidative stress, integrating human relevance through archived colon tissues from New Mexico's
diverse and underprivileged population, as well as human colonoids (both normal and tumor, Aim 3). These
goals aim to enhance our comprehension of the fundamental mechanisms underlying microplastics' toxicity
and identify actionable elements for community-level disease prevention and treatment.

## Key facts

- **NIH application ID:** 10982259
- **Project number:** 1R01ES035780-01A1
- **Recipient organization:** UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
- **Principal Investigator:** Xiang Xue
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $453,688
- **Award type:** 1
- **Project period:** 2024-08-16 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10982259

## Citation

> US National Institutes of Health, RePORTER application 10982259, Mechanisms for environmental microplastics-enhanced colorectal tumor progression (1R01ES035780-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10982259. Licensed CC0.

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