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Peer-reviewedCC BY 4.0Molecular Biology of the Cell

Reversibility of nuclear and 3D genomic changes in non-cancerous fibroblasts after constricted migration

  • Christopher Playter1
  • Samuel John Benson1
  • Renata Dos Reis Marques2
  • Preston Young3
  • Timothy B. Simmons1
  • Kathryn Perry1
  • Amanda K. Swets1
  • Amit S. Joshi1
  • Rachel Patton McCord1
  1. 1Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee, 37996
  2. 2Biomedical Engineering, University of Tennessee, Knoxville, TN, 37996
  3. 3Mechanical Engineering, University of Tennessee, Knoxville, TN, 37996
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Abstract

Metastatic cancer cells and healthy fibroblasts must traverse constrictive spaces to reach secondary sites. After passing through multiple constrictions, cancer cells often experience stable changes to their nuclear morphology, 3D genome structure, and migratory phenotype. Here, we investigate whether fibroblasts (BJ-5ta), which are non-cancerous and have an inherent ability to migrate to fulfill roles in wound repair, likewise experience nuclear and 3D genomic changes with constricted migration. We find that BJ-5ta cells only slightly increase their migratory capacity after sequential constricted migrations but do experience nuclear deformations and 3D genome alterations at the compartment level after constricted migration. Transient compartment shifts spatially rearranged genes associated with preparation for and response to migration. Unlike the stable changes associated with long term phenotype changes in cancer cells, however, the nuclear deformations recovered to unmigrated levels following proliferation and cell movement. Some compartment changes persist and might influence responses to future stimuli, but most 3D genome changes revert to the unmigrated state after cell proliferation. Our study shows that non-cancerous migratory cells are not necessarily less susceptible to nucleus and 3D genome alterations caused by constricted migration, but do recover from such alterations more readily than cancer cells.

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Cite

BibTeXRIS
BibTeX
@article{playter2026reversibility,
  title = {{Reversibility of nuclear and 3D genomic changes in non-cancerous fibroblasts after constricted migration}},
  author = {Christopher Playter and Samuel John Benson and Renata Dos Reis Marques and Preston Young and Timothy B. Simmons and Kathryn Perry and Amanda K. Swets and Amit S. Joshi and Rachel Patton McCord},
  journal = {Molecular Biology of the Cell},
  year = {2026},
  month = oct,
  doi = {10.1091/mbc.e26-01-0053},
  url = {https://doi.org/10.1091/mbc.e26-01-0053},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Reversibility of nuclear and 3D genomic changes in non-cancerous fibroblasts after constricted migration
AU  - Christopher Playter
AU  - Samuel John Benson
AU  - Renata Dos Reis Marques
AU  - Preston Young
AU  - Timothy B. Simmons
AU  - Kathryn Perry
AU  - Amanda K. Swets
AU  - Amit S. Joshi
AU  - Rachel Patton McCord
PY  - 2026
DA  - 2026/10/26
JO  - Molecular Biology of the Cell
DO  - 10.1091/mbc.e26-01-0053
UR  - https://doi.org/10.1091/mbc.e26-01-0053
AB  - Metastatic cancer cells and healthy fibroblasts must traverse constrictive spaces to reach secondary sites. After passing through multiple constrictions, cancer cells often experience stable changes to their nuclear morphology, 3D genome structure, and migratory phenotype. Here, we investigate whether fibroblasts (BJ-5ta), which are non-cancerous and have an inherent ability to migrate to fulfill roles in wound repair, likewise experience nuclear and 3D genomic changes with constricted migration. We find that BJ-5ta cells only slightly increase their migratory capacity after sequential constricted migrations but do experience nuclear deformations and 3D genome alterations at the compartment level after constricted migration. Transient compartment shifts spatially rearranged genes associated with preparation for and response to migration. Unlike the stable changes associated with long term phenotype changes in cancer cells, however, the nuclear deformations recovered to unmigrated levels following proliferation and cell movement. Some compartment changes persist and might influence responses to future stimuli, but most 3D genome changes revert to the unmigrated state after cell proliferation. Our study shows that non-cancerous migratory cells are not necessarily less susceptible to nucleus and 3D genome alterations caused by constricted migration, but do recover from such alterations more readily than cancer cells.
SN  - 1059-1524
SN  - 1939-4586
ER  -