# Passive nuclear transport deviates from Fickian behavior in prostate and breast cell types

**Authors:** Nicholas R. Scott, Alexander J. Lin, Brian Belardi, Sapun H. Parekh

PMC · DOI: 10.1080/19491034.2026.2620223 · Nucleus · 2026-01-31

## TL;DR

This study shows that passive nuclear transport in prostate and breast cells does not follow standard diffusion rules and changes with cell type and cancer-like transformations.

## Contribution

The paper reveals non-Fickian nuclear transport behavior and its alteration with cancer-related phenotypic changes.

## Key findings

- Passive nuclear uptake does not consistently depend on molecular weight, indicating non-Fickian behavior.
- TGF-Beta treatment alters nuclear transport in breast cells to resemble invasive cancer cells.
- Nuclear permeability changes are linked to cancerous cellular transformation.

## Abstract

Nuclear trafficking is essential for cellular function and biomedical applications such as nucleus-targeted drug delivery; however, how passive nuclear transport varies across cell types and phenotypic states remains poorly understood. Here, we investigate passive nuclear transport of fluorescent molecular cargoes spanning 500–20,000 Da across multiple cell lines. We observe cell-line-specific nuclear restrictions and find that passive nuclear uptake does not exhibit a monotonic dependence on molecular weight, suggesting non-Fickian transport behavior. Furthermore, transforming a healthy breast cell model into an invasive-like phenotype via TGF-Beta treatment significantly altered passive nuclear transport characteristics, closely resembling those of a well-established invasive breast cancer cell line. These phenotype-dependent changes in nuclear permeability provide new insight into fundamental biophysical alterations associated with cancerous cellular transformation.

## Linked entities

- **Chemicals:** TGF-Beta (PubChem CID 56842206)
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** TUBA1B (tubulin alpha 1b) [NCBI Gene 10376] {aka K-ALPHA-1}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, NUP153 (nucleoporin 153) [NCBI Gene 9972] {aka HNUP153, N153}, LMNA (lamin A/C) [NCBI Gene 4000] {aka CDCD1, CDDC, CMD1A, CMT2B1, EMD2, FPL}, EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG}, RGPD2 (RANBP2 like and GRIP domain containing 2) [NCBI Gene 729857] {aka NUP358, RANBP2L2, RGP2, ranBP2-like 2}, SNAP91 (synaptosome associated protein 91) [NCBI Gene 9892] {aka AP180, CALM}, PRPH2 (peripherin 2) [NCBI Gene 5961] {aka AOFMD, AVMD, CACD2, DS, MDBS1, RDS}
- **Diseases:** breast cancer (MESH:D001943), oncogenesis (MESH:D063646), breast (MESH:D061325), male prostate cancer (MESH:D011471), cancer (MESH:D009369), invasive (MESH:D009361), NPC (MESH:D052556), fibrocystic (MESH:D054990), infection (MESH:D007239)
- **Chemicals:** NaCl (MESH:D012965), H2O (MESH:D014867), HEPES (MESH:D006531), DOPC (MESH:C017251), cholesterol (MESH:D002784), Dextran (MESH:D003911), PBS (MESH:D007854), Rhodamine PE (MESH:C053685), Digitonin (MESH:D004072), F12 (MESH:C007782), paraformaldehyde (MESH:C003043), carboxylic-acid (MESH:D002264), Alexa-647 (MESH:C569686), DOX (MESH:D004317), Alexa-488 (-), hydrocortisone (MESH:D006854), glucose (MESH:D005947), sugar (MESH:D000073893), HCl (MESH:D006851), phenol-red (MESH:D010637), Lipids (MESH:D008055), Ca (MESH:D002118)
- **Species:** Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Mycoplasma (genus) [taxon 2093]
- **Cell lines:** MCF-10A — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0598), MT21031CV — Homo sapiens (Human), Transformed cell line (CVCL_HN84), WPE1-NA22 — Homo sapiens (Human), Transformed cell line (CVCL_3810), HTB — Mus musculus (Mouse), Hybridoma (CVCL_A8FQ), PC3 — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_0035), MDA-MB-231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062)

## Full text

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## Figures

50 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12867411/full.md

## References

47 references — full list in the complete paper: https://tomesphere.com/paper/PMC12867411/full.md

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Source: https://tomesphere.com/paper/PMC12867411