# Discovering proteins that explain single-cell heterogeneity in fibrillar migration

> **NIH NIH R21** · NORTHEASTERN UNIVERSITY · 2021 · $220,193

## Abstract

Project Summary
The daunting heterogeneity of breast cancer is apparent even within a tumor in an individual patient. The
clinical consequence is that a targeted therapeutic e ective against some cancer cells remains impotent
against counterparts that have evolved alternative pathways to accomplish disease-driving functions.
Thus, there is an urgent need for single-cell approaches to discover molecular targets that span the
complementary pathways by which heterogeneous cancer cells metastasize. An early step in metastasis
involves cancer cells invading through the primary tumor microenvironment to reach nearby vascular and
lymphatic networks through which they disseminate to secondary sites. A common mode of breast cancer
invasion in the primary tumor microenvironment involves cancer cell migration along collagen bers. The
proteins that regulate brillar migration are poorly understood, and the diversity of pathways by which
breast cancer subtypes accomplish this invasive mode of migration remains to be elucidated. In the
proposed work, we seek to develop, optimize and apply single-cell migration and proteomics (scMAP),
an innovative method to quantify both the migration properties and the proteome of the same individual
cell. Thus, scMAP enables the collection of a novel data set that directly links cell migration and the
abundance of thousands of proteins at the single-cell level. We will apply scMAP to discover proteins
whose abundance is associated with enhanced brillar migration of a panel of heterogenous breast cancer
cell lines. Analysis of this novel data set by total least squares regression and mutual information
will reveal proteins that exhibit quantitative linear and non-linear relationships to brillar migration
properties. These results will identify distinct sets of proteins that explain the disparate brillar migration
properties of heterogeneous breast cancer cells. The identi ed proteins feed a pipeline for future functional
testing in complex 3d brillar matrices and subsequent potential therapeutic application to curb brillar
invasive migration. In addition, scMAP opens the door to proteomic-scale, single-cell resolution insights
into cell migration in other contexts, including other modes of motility in metastasis.

## Key facts

- **NIH application ID:** 10133558
- **Project number:** 5R21CA246150-02
- **Recipient organization:** NORTHEASTERN UNIVERSITY
- **Principal Investigator:** ANAND R ASTHAGIRI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $220,193
- **Award type:** 5
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133558

## Citation

> US National Institutes of Health, RePORTER application 10133558, Discovering proteins that explain single-cell heterogeneity in fibrillar migration (5R21CA246150-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10133558. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*