# Arp2/3 complex heterogeneity as a target for metastatic cancer

> **NIH NIH P20** · DARTMOUTH COLLEGE · 2022 · $262,400

## Abstract

During metastasis, cancer cells can break free from primary tumor sites and migrate into the extracellular 
matrix, through the basement membrane, travel in the blood or lymph, and settle in distant sites. Actin 
reorganization, specifically in branched actin networks at the leading edge, is responsible for cell motility at 
various stages of these metastatic processes. A seven-protein complex called the Arp2/3 complex is 
responsible for the new actin filament growth and branching at the leading edge required for motility and 
proteins in this complex are often upregulated in cancer. In addition to this transcriptional upregulation, 
microRNAs can also control expression Arp2/3 complex components, affecting migratory potential. One protein 
in particular, ARPC5, is known to be regulated transcriptionally and by miRNAs in many cancers including 
head and neck squamous cell carcinoma, non-small cell lung cancer, bladder cancer, colorectal cancer, breast 
cancer, renal cell carcinoma, and prostate cancer, suggesting its key role in cancer cell migration. Given the 
endogenous suppression of expression by miRNAs and also the possible expression of an alternate isoform of 
ARPC5, ARPC5L, we propose that Arp2/3 complexes with no ARPC5, ARPC5, or ARPC5L can create 
versions of the actin-binding complex that are tuned for various cell functions. To address this, in Aim 1, we will 
purify and perform in vitro and in vivo characterization of complexes from a model system that naturally lacks 
ARPC5, a green alga that performs other typical Arp2/3 functions outside of surface motility. In Aim 2, we will 
directly test the functional consequences of ARPC5 and/or ARPC5L deletion in triple negative breast cancer 
cell line isolates that vary in their migration potential. Successful completion of this project will determine 
the molecular and cellular consequences of ARPC5-dependent Arp2/3 composition as well as the 
potential impact of modulating ARPC5 composition in the context of metastatic cancer. The BioMT 
COBRE will provide essential mentoring and collaboration from experts with decades of actin biochemistry and 
specifically Arp2/3 experience as well as in tumor progression. The COBRE will also provide core facility 
support in biochemistry and microscopy for the completion of these aims. Ultimately, this will allow the PI to 
expand work from her lab outside core projects in microtubule-based cytoskeletal structures into a new area of 
investigation related to actin regulation.

## Key facts

- **NIH application ID:** 10460277
- **Project number:** 5P20GM113132-07
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** PRACHEE AVASTHI
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $262,400
- **Award type:** 5
- **Project period:** 2016-05-15 → 2021-08-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10460277

## Citation

> US National Institutes of Health, RePORTER application 10460277, Arp2/3 complex heterogeneity as a target for metastatic cancer (5P20GM113132-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10460277. Licensed CC0.

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