Effects of Mechanical Pressure on Liver Cancer Cells: Promoting Invasion and Drug Resistance

Recent studies by Yale Cancer Center researchers have shed light on how physical forces within the tumor environment influence liver cancer progression. Liver tumors, especially in fibrotic, stiff tissues, generate significant mechanical compression on the cancer cells due to dense tissue matrices and rapid growth. This physical stress leads to notable changes in cellular behavior, including increased invasion, drug resistance, and shifts in gene activity.

To explore this phenomenon, scientists developed both computational and laboratory models to simulate the mechanical pressures experienced by tumor cells in vivo. In these experiments, applying controlled compression—either through weights or hyperosmotic media—revealed that such mechanical stress prompts extensive transcriptional changes. Specifically, there was a reduction in liver-specific gene markers alongside an increase in genes associated with cancer progression.

Further analysis identified that compression activates Rac1, a protein involved in cellular protrusion formation, facilitating migration and invasion. Additionally, mechanotransduction prompted YAP, a key regulator of gene expression, to relocate to the nucleus—supporting cancer cell survival under pressure. The studies also show that compression affects calcium signaling within cells, contributing to resistance against apoptosis.

Crucially, even short-term compression was enough to make liver cancer cells more aggressive and resistant to drugs, highlighting the importance of considering physical forces in cancer treatment strategies. Targets such as Rac1 pathways and calcium signaling may offer new therapeutic avenues to combat compression-adapted tumor cells.

These insights underscore the role of mechanical forces in cancer growth and metastasis, pointing toward integrated approaches that tackle both biological and physical tumor components. Understanding how pressure influences tumor behavior can lead to more effective therapies for liver cancer and other solid tumors.

Source: https://medicalxpress.com/news/2025-05-liver-cancer-cells-pressure-compression.html