# Ferroportin Repression in Head and Neck Squamous Cell Carcinoma

> **NIH NIH F32** · VIRGINIA COMMONWEALTH UNIVERSITY · 2020 · $70,492

## Abstract

Project Summary
Iron is an essential element that is required in nearly all living organisms. Due to its gas binding and redox
properties it plays an irreplaceable role in human physiology helping to facilitate the reactions necessary to
sustain life. Ferroportin (FPN) acts as the sole iron efflux protein in humans, and all iron transport to the plasma
occurs through this single channel. Thus, FPN plays a critical role in the maintenance of human iron homeostasis.
The regulatory hormone hepcidin controls the levels of membrane associated FPN through the induction of
endocytosis and proteasomal degradation via direct binding. Despite its importance to host physiology, very little
is known about the role FPN, and iron homeostasis, plays in progression of head and neck cancers. Preliminary
work shows that FPN is expressed in normal cells of the oral cavity (oral keratinocytes and gingival fibroblasts).
We show repression of FPN and de-regulation of iron homeostasis occurs in advanced (metastatic) head and
neck squamous cell carcinoma (HNSCC). Preliminary data also reveals that cell lines with reduced ferroportin
levels may make cells more sensitive to ferroptosis. Immunoblots reveal the expression of hepcidin in HNSCC
cell lines, indicating that aberrant hepcidin expression may play a role in ferroportin repression in these cell types.
The goal of this proposal is to investigate the role FPN repression plays in the progression of HNSCC. We will
also probe the interaction of FPN and hepcidin through Small Angle X-ray scattering (SAXS) to shed light on the
molecular mechanisms of hepcidin mediated repression of FPN. In aim 1 we will investigate the clinicopathology
of FPN repression in HNSCC. We will modulate ferroportin levels in HNSCC cell lines and observe the effect it
has on cell proliferation, metastatic potential, and sensitivity to ferroptosis. In aim 2 we will we will explore the
role hepcidin plays in the repression of FPN and investigate the allosteric mechanisms of the hepcidin-FPN
interaction using SAXS. The findings in this study, despite the outcomes, will be important in characterizing the
role iron homeostasis plays in oral health and disease. This fellowship training plan will provide the applicant
experience in the fields of cell and cancer biology as well as in the handling and purification of membrane
proteins. Training of the applicant will be sponsored by mentors with expertise in the fields of iron biology and
cancer biology, as well as in an environment with other trainees.

## Key facts

- **NIH application ID:** 9992183
- **Project number:** 1F32DE029412-01A1
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Benjamin Ross Belvin
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $70,492
- **Award type:** 1
- **Project period:** 2020-03-25 → 2023-03-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9992183

## Citation

> US National Institutes of Health, RePORTER application 9992183, Ferroportin Repression in Head and Neck Squamous Cell Carcinoma (1F32DE029412-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9992183. Licensed CC0.

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