# Exosomes in HNSCC Progression

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2024 · $470,032

## Abstract

Exosomes are small extracellular vesicles (EVs) that are secreted from multivesicular
endosomes (MVE) and have been recently recognized to promote cancer metastasis.
Exosomes carry bioactive proteins, lipids and nucleic acids and are an important but poorly
understood component of the tumor microenvironment. We recently discovered that actin-rich
invasive structures called invadopodia are key docking sites for MVE in cancer cells, leading to
enhanced exosome secretion. Furthermore, we found that the key invadopodia regulator
cortactin enhances MVE docking and exosome secretion. Notably, cortactin is gene amplified
and overexpressed in a number of cancers, especially in head and neck squamous cell
carcinoma (HNSCC). Furthermore, cortactin overexpression in HNSCC is correlated with
decreased patient survival and increased metastasis. Based on these data, we hypothesize that
cortactin overexpression drives poor prognosis in HNSCC due to its key role in
promoting exosome secretion. Furthermore, we hypothesize that key exosome cargoes
synergize with cortactin to promote tumor-induced angiogenesis, lymphangiogenesis,
and metastasis. Specifically, we have identified EphB-ephrinB signaling as a key angiogenic
axis regulated by HNSCC-secreted exosomes. Thus, we propose that both the number and
molecular cargo of exosomes drive aggressive HNSCC behavior in a synergistic manner. We
will test these hypotheses and leverage our work to identify potential exosomal blood-and
tissue-based biomarkers of regional and distant metastasis.

## Key facts

- **NIH application ID:** 10880239
- **Project number:** 5R01CA249684-04
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Alissa M Weaver
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $470,032
- **Award type:** 5
- **Project period:** 2021-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10880239

## Citation

> US National Institutes of Health, RePORTER application 10880239, Exosomes in HNSCC Progression (5R01CA249684-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10880239. Licensed CC0.

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