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Differential Sensitivity to MEK Inhibitors Highlights Distinct Entosis Mechanisms in BxPC3 and MCF7 Cells
Paweł Tyrna1,2, Julia Kostro1, Monika Olszanecka1
1Histology and Embryology Students' Science Association, Department of Histology and Embryology, Faculty of Medicine, Medical University of Warsaw, Chalubinskiego 5, 02-004 Warsaw, Poland.
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.
Insights
MEK pathway inhibition significantly reduced entosis in pancreatic cancer cells (BxPC3) but not breast cancer cells (MCF7), indicating cell-type-specific regulation of this cancer cell-in-cell process.
Area of Science:
- Cell Biology
- Cancer Research
- Molecular Biology
Background:
- Entosis is a cell-in-cell phenomenon crucial in epithelial cancers.
- It involves cell detachment, adhesion, and internalization, driven by actomyosin contractility.
- Understanding entosis regulation is key to cancer therapy.
Purpose of the Study:
- To investigate the effect of MEK pathway inhibition on entosis.
- To determine if MEK inhibition impacts entosis differently in various cancer cell types.
Main Methods:
- Utilized a functional assay with differentially stained cell populations to assess entosis.
- Examined MEK pathway inhibition in BxPC3 (pancreatic) and MCF7 (breast) cancer cell lines.
- Evaluated pharmacological interventions on inner and outer cells during entosis.
Main Results:
- MEK inhibition significantly reduced the entotic index in BxPC3 cells.
- MCF7 cells showed no selective reduction in entosis with MEK inhibitors.
- BxPC3 cells' reliance on adhesion correlated with reduced entosis upon MEK inhibition.
Conclusions:
- Entosis regulation is cell-type-specific.
- MEK pathway inhibition differentially affects entosis in epithelial cancers.
- Differences may relate to protrusion formation and Ras signaling pathways.
