# Deconstructing fast amoeboid cell migration

> **NIH NIH R35** · STATE UNIVERSITY NEW YORK STONY BROOK · 2024 · $395,387

## Abstract

Project Summary
Many cells can travel from one place to another. This nomadic cell behavior is harnessed to form organs, seal
wounds, and hunt down pathogens, but it is often dysregulated in human diseases, including cancer.
Consequently, understanding the molecular basis of cell movement has widespread significance for human
health. Decades of cell migration studies have outlined how a cell moves on a flat surface. In a two-dimensional
environment, a moving cell extends a branched actin-filled protrusion in the direction of movement, while
actomyosin contractility retracts the rear. However, cells can move without actin-filled protrusions in vivo using
a poorly understood, three-dimensional migration mode called amoeboid migration. Amoeboid migrating cells
can move by extruding pressure-filled blebs devoid of actin or rapidly migrate with a near-constant spherical
shape using cortical actin flow. Cortical flow-driven amoeboid migration is commonly referred to as fast amoeboid
migration (FAM) and is induced by mechanical confinement in a wide variety of cells, with an increased
propensity in invasive cancer cells. The non-genetic and extensive induction of FAM, coupled with its use by
cancer cells in vivo, necessitates a mechanistic understanding of its underpinnings. However, observing and
perturbing FAM is technically challenging in vivo, and the plasticity with which cells can switch how they migrate
can confound subsequent analysis. My lab uses the developmental migration of Drosophila primordial germ cells
(PGCs) as a facile, reproducible system to study FAM. PGCs natively use FAM in vivo and, importantly, maintain
the characteristic cortical actin flows that power FAM outside of the embryo in culture without mechanochemical
inputs. Thus, PGCs do not alter how they move, even in a foreign two-dimensional environment. Over the next
five years, we will capitalize on the inflexible nature of migratory PGCs to deconstruct FAM and address several
outstanding, currently intractable questions: (1) What cortical actin architectures are permissive for cortical flows,
and how are these networks assembled, regulated, and maintained? (2) How are cortical flows oriented by
guidance cues to direct FAM? (3) How are cortical flows transmitted to a given substrate to generate traction for
productive motility? Results from this study will shed light on a poorly understood cell migration strategy and will
identify key factors to not only halt it for therapeutic intervention but also endow other cells with its use for cell-
based therapies.

## Key facts

- **NIH application ID:** 11020628
- **Project number:** 1R35GM157022-01
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Benjamin C Lin
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $395,387
- **Award type:** 1
- **Project period:** 2024-09-16 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11020628

## Citation

> US National Institutes of Health, RePORTER application 11020628, Deconstructing fast amoeboid cell migration (1R35GM157022-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11020628. Licensed CC0.

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