# Differential Sensitivity to MEK Inhibitors Highlights Distinct Entosis Mechanisms in BxPC3 and MCF7 Cells

## TL;DR

This study shows that MEK inhibitors affect entosis differently in pancreatic and breast cancer cells, suggesting distinct mechanisms.

## Contribution

The study reveals cell-type-specific regulation of entosis through MEK inhibition in BxPC3 and MCF7 cancer cells.

## Key findings

- MEK inhibition significantly reduced entosis in BxPC3 pancreatic cancer cells.
- MCF7 breast cancer cells showed no entotic response to three MEK inhibitors.
- Entosis regulation may involve differences in protrusion formation and Ras signaling.

## Abstract

Entosis is a form of cell-in-cell interaction observed in epithelial cancers, characterized by the internalization of one cell into another. This process is initiated by cell detachment, cadherin-mediated homotypic adhesion, and the formation of an entotic vacuole. Mechanistically, entosis is driven by Rho/ROCK signaling and actomyosin contractility in the invading (inner) cell, which becomes stiffer and is pulled into the softer host (outer) cell. A functional assay using differently stained cell populations allows for the assessment of pharmacological interventions on either the inner or outer cell during entosis. In this study, we investigated the impact of MEK pathway inhibition on entosis in two epithelial cancer cell lines, BxPC3 (pancreatic cancer) and MCF7 (breast cancer). BxPC3 cells, which rely on adhesion, exhibited a significant reduction in entotic index upon MEK inhibition. In contrast, MCF7 cells showed no selectivity of entosis to three different MEK inhibitors. These findings suggest cell-type-specific regulation of entosis, potentially linked to differences in protrusion formation mechanisms and upstream Ras signaling pathways previously implicated in cancer cell motility.