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Updated: Sep 1, 2025
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Revealing the Cytoskeletal Organization of Invasive Cancer Cells in 3D
Published on: October 26, 2013
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Constricted migration is associated with stable 3D genome structure differences in cancer cells
Rosela Golloshi1, Christopher Playter1, Trevor F Freeman1
1Biochemistry & Cellular and Molecular Biology Department, University of Tennessee, Knoxville, TN, USA.
EMBO Reports
|August 15, 2022
Summary
Cancer cells change their 3D genome structure to efficiently migrate through constrictions. These epigenetic changes in chromosome structure stably alter gene expression and enhance cell migration, aiding metastasis.
Area of Science:
- Cell Biology
- Genomics
- Cancer Research
Background:
- Metastatic cancer cells must deform their nuclei to navigate through constrictions.
- Nuclear structure, including chromosome organization, influences cell mechanics, gene regulation, and DNA repair.
Purpose of the Study:
- To investigate the relationship between 3D genome structure and constricted cell migration in cancer.
- To identify stable phenotypic and genomic alterations in cancer cells following constricted migration.
Main Methods:
- Utilized melanoma (A375) and breast cancer (MDA-MB-231) cell lines.
- Employed Hi-C experiments to analyze 3D genome architecture.
- Assessed cellular morphology, migration efficiency, and gene expression patterns.
Main Results:
- Cells surviving constricted migration showed increased efficiency, elongated morphology, and altered Lamin A/C and heterochromatin distribution.
- Hi-C revealed distinct chromosome spatial compartmentalization and altered gene expression related to migration and metastasis.
- Consistent changes in 3D genome structure, including reduced B compartment interaction, were observed post-constriction.
Conclusions:
- Passage through constrictions induces or selects for specific 3D genome structure changes.
- These structural alterations may epigenetically encode stable changes in gene expression and cellular migration phenotype.
- Findings suggest a mechanism for how cancer cells adapt for enhanced metastatic potential.
Keywords:
Hi-Cchromosome spatial compartmentalizationconstricted migrationnuclear laminanucleus deformationMore Related Videos
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