# Molecular mechanisms underlying circulating tumor cell aggregation

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2022 · $358,680

## Abstract

Circulating tumor cells (CTCs) pose continuous and persistent threats to create new metastases albeit at an
unknown, extremely low efficiency. Compared to single CTCs, clusters of multicellular CTCs possess 20-100
times higher metastatic capacity, create more polyclonal metastasis, and correlate with worse prognosis. Our
previous studies identified that in addition to collective migration and cohesive shedding, tumor cell aggregation
is a new mechanism for CTC cluster formation, enhancing cancer stemness and polyclonal metastasis. The
objectives of this proposal are to elucidate the molecular mechanisms underlying CD44 and PAK2-promoted
CTC aggregation, identify the drivers of CTC cluster-mediated polyclonal metastasis, and therefore develop
proof-of-principle targeting strategies to block lung metastasis of triple negative breast cancer, using multiple
human PDXs and CTC lines as well as mouse tumor models. The collaborative team includes Dr. Huiping Liu
(Northwestern University) with expertise in CTC and cancer stemness, breast oncologist Dr. Massimo
Cristofanilli (Northwestern University), imaging expert Dr. Constadina Arvanitis (Northwestern University), and
bioinformaticist and structural biologist Dr. Yang Shen (Texas A & M).

## Key facts

- **NIH application ID:** 10372102
- **Project number:** 5R01CA245699-03
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Huiping Liu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $358,680
- **Award type:** 5
- **Project period:** 2020-04-11 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10372102

## Citation

> US National Institutes of Health, RePORTER application 10372102, Molecular mechanisms underlying circulating tumor cell aggregation (5R01CA245699-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10372102. Licensed CC0.

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