# Impact of ionizing radiation on cell-ECM mechanical crosstalk in breast cancer

**Authors:** Rocco Mottareale, Crescenzo Frascogna, Giuseppe La Verde, Cecilia Arrichiello, Paolo Muto, Paolo A. Netti, Sabato Fusco, Valeria Panzetta, Mariagabriella Pugliese

PMC · DOI: 10.3389/fbioe.2024.1408789 · Frontiers in Bioengineering and Biotechnology · 2024-06-06

## TL;DR

This study explores how ionizing radiation affects the mechanical interactions between breast cancer cells and their surrounding environment, revealing changes in cell stiffness and structure.

## Contribution

The study reveals how radiation alters cell mechanics and focal adhesions in breast cancer cells on stiff substrates.

## Key findings

- Ionizing radiation increases paxillin-rich focal adhesions and cytoskeleton structuration in adenocarcinoma cells.
- Radiation-induced cell stiffness affects cytoplasmic and nuclear morphologies on stiff substrates.
- Mechanical and radiation interplay could lead to new clinical strategies for breast cancer.

## Abstract

The stiffness of the extracellular matrix plays a crucial role in cell motility and spreading, influencing cell morphology through cytoskeleton organization and transmembrane proteins’ expression. In this context, mechanical characterization of both cells and the extracellular matrix gains prominence for enhanced diagnostics and clinical decision-making. Here, we investigate the combined effect of mechanotransduction and ionizing radiations on altering cells’ mechanical properties, analysing mammary cell lines (MCF10A and MDA-MB-231) after X-ray radiotherapy (2 and 10 Gy). We found that ionizing radiations sensitively affect adenocarcinoma cells cultured on substrates mimicking cancerous tissue stiffness (15 kPa), inducing an increased structuration of paxillin-rich focal adhesions and cytoskeleton: this process translates in the augmentation of tension at the actin filaments level, causing cellular stiffness and consequently affecting cytoplasmatic/nuclear morphologies. Deeper exploration of the intricate interplay between mechanical factors and radiation should provide novel strategies to orient clinical outcomes.

## Linked entities

- **Proteins:** LOC575064 (leupaxin)
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** PXN (paxillin) [NCBI Gene 5829]
- **Diseases:** breast cancer (MESH:D001943), adenocarcinoma (MESH:D000230)
- **Cell lines:** MDA-MB-231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062), MCF10A — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0598)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11187264/full.md

## References

60 references — full list in the complete paper: https://tomesphere.com/paper/PMC11187264/full.md

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Source: https://tomesphere.com/paper/PMC11187264