# The role of nuclear envelope rupture and repair in cell function and metastasis

> **NIH NIH F32** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $24,457

## Abstract

PROJECT SUMMARY/ABSTRACT
In the cell, genetic information is tightly regulated and maintained through functions of the nuclear envelope
(NE). The NE is composed of a double membrane and a network of proteins that sequester and protect the
genome inside the nucleus, compartmentalized away from the bulk of cellular processes. One important
function of the NE is to structurally shield the genome from physical forces. In addition, the NE controls the
transport of material in and out of the nucleus and regulates gene expression by directing interactions between
genes and proteins. Defects in NE protein expression alter NE organization, structure, and dynamics leading to
changes in gene expression and genome instability. NE protein dysregulation is implicated in severe diseases
including dilated cardiomyopathy, muscular dystrophy, progeria, and cancers. It was recently discovered that in
some cancer cell types the NE can rupture and reseal during unexpected points of the cell cycle. Some cells
undergo repeated NE rupture and repair events without a decrease in viability, and migrating cells routinely
rupture and repair the NE. This discovery has altered the canonical model of the interphase NE and introduced
a role for aberrant NE dynamics in the pathology of diseases like cancer. Despite its importance, the
mechanisms that control NE dynamics and their dysregulation in disease are largely unknown. We hypothesize
that NE rupture and repair mechanisms contribute to cancer by aiding the biomechanics of single cell
migration. The goal of this project is to determine the molecular mechanisms underlying NE dynamics and
address how changes in the organization or stability of the nuclear envelope relates to cancer development.
We aim to: 1. Identify mechanisms of NE rupture and repair, 2. Determine the consequences of NE rupture
and repair on the cell, and 3. Define the role of NE rupture and repair in cancer cell migration. Questions of
why the NE ruptures and how it is repaired will be addressed using a cell-based model of this process and a
live-cell imaging platform developed in the lab. We will refine the link between dynamic NE rupture and cancer
by observing how rupture and repair affect cancer cell function, growth, and migration. Through this work we
hope to identify the factors that control NE rupture and repair and uncover biomarkers for cancer cell
progression with the ultimate goal of forestalling cancer progression and treating disease. Understanding the
complex functions of the NE and its dysregulation will provide important clues about disease pathogenesis and
human aging.

## Key facts

- **NIH application ID:** 9931173
- **Project number:** 5F32CA232764-03
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Alexandra Marie Young
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $24,457
- **Award type:** 5
- **Project period:** 2018-07-03 → 2020-11-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9931173

## Citation

> US National Institutes of Health, RePORTER application 9931173, The role of nuclear envelope rupture and repair in cell function and metastasis (5F32CA232764-03). Retrieved via AI Analytics 2026-06-23 from https://api.ai-analytics.org/grant/nih/9931173. Licensed CC0.

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