# Loss of Hormone Receptor Expression after Exposure to Fluid Shear Stress in Breast Cancer Cell Lines

## TL;DR

This study shows that fluid shear stress, experienced during cancer metastasis, can reduce hormone receptor expression in breast cancer cells, potentially leading to more aggressive cancer.

## Contribution

The study introduces a novel microfluidic platform to investigate how fluid shear stress affects hormone receptor signaling in breast cancer cells.

## Key findings

- Fluid shear stress alters the expression of 540 proteins and 1473 phospho-proteins in breast cancer cells.
- Exposure to fluid shear stress represses estrogen receptor and estrogen-mediated gene expression.
- Fluid shear stress increases mTOR phosphorylation in breast cancer cells.

## Abstract

Following metastatic spread, many hormone receptor positive (HR+) patients develop a more aggressive phenotype with an observed loss of the HRs estrogen receptor (ER) and progesterone receptor (PR). During metastasis, breast cancer cells are exposed to high magnitudes of fluid shear stress (FSS). Unfortunately, the role for FSS on the regulation of HR expression and function during metastasis is not fully understood. This study was designed to elucidate the impact of FSS on HR+ breast cancer. Utilizing a microfluidic platform capable of exposing breast cancer cells to FSS that mimics in situ conditions, we demonstrate the impact of FSS exposure on representative HR+ breast cancer cell lines through protein and gene expression analysis. Proteomics results demonstrated that 540 total proteins and 1473 phospho-proteins significantly changed due to FSS exposure and pathways of interest included early and late estrogen response. The impact of FSS on response to 17β-estradiol (E2) was next evaluated and gene expression analysis revealed repression of ER and E2-mediated genes (PR and SDF1) following exposure to FSS. Western blot demonstrated enhanced phosphorylation of mTOR following exposure to FSS. Taken together, these studies provide initial insight into the effects of FSS on HR signaling in metastatic breast cancer.