# Material Stiffness Directs Oral Cancer Migration

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $392,187

## Abstract

Project Summary
Oral squamous cell carcinoma (OSCC) is the sixth most common epithelial cancer worldwide with 50,000 new
cases/year in US. Despite being less frequent, survival rates are relative lower. Clinically, OSCC presents as a
necrotic lesion with stiffened borders; surgical resection requires significant tissue loss up to 2 cm surround the
lesion, owing to the fact that these tumors are poorly margined and require significant resection to ensure all
metastatic disease is removed. Even with aggressive surgical approaches, significant morbidity and mortality is
associated with OSCC, and this dramatically reduces patient quality of life. While stiffened borders are a hallmark
of the disease, it is unclear to what extent microenvironmental properties, e.g., mechanical changes in
extracellular matrix (ECM) stiffness, contribute to tumor progression and invasion. The role of stiffness has been
well established in other epithelial tumors, e.g., breast, but our understanding in OSCC is relatively nascent; less
than 10 studies have even peripherally addressed the issue. Preliminary data from our groups is the first to
demonstrate that a stiffer environment induces epithelial-to-mesenchymal transition (EMT) of oral epithelial cells
and that they adopt a more aggressive behavior of invasive OSCC (Matte et al 2019; Moon et al 2023). EMT of
these oral tissues might contribute to frequent tumor recurrence observed in patients with excessively stiff tumor
margins. Since OSCC is exceedingly invasive, learned behaviors within the stiffened tumor must be remembered
and recalled once in softer adjacent oral tissues to facilitate the establishment of secondary disease. Thus, we
hypothesize that tumor stiffness induces the acquisition and consolidation of mechanical memory, i.e., EMT and
migration, which can be recalled later when the resulting OSCC cells disseminate and contribute to tumor
metastasis, invasion, and recurrence. To test this hypothesis, we propose the following specific aims:
Specific Aim 1: Elucidate the mechanisms involved in mechanical sensing leading to “memory” acquisition and
recall
Specific Aim 2: Determine to what extent epigenetic changes in OSCC induce “memory” consolidation

## Key facts

- **NIH application ID:** 10883331
- **Project number:** 1R01CA280279-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Adam J Engler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $392,187
- **Award type:** 1
- **Project period:** 2024-07-08 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10883331

## Citation

> US National Institutes of Health, RePORTER application 10883331, Material Stiffness Directs Oral Cancer Migration (1R01CA280279-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10883331. Licensed CC0.

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