Mechano-metabolism of metastatic breast cancer cells in 2D and 3D microenvironments.
Anuja JaganathanJoshua TothXingyu ChenRamin BasirLaurent PieuchotYihui ShenCynthia Reinhart-KingVivek B ShenoyPublished in: bioRxiv : the preprint server for biology (2024)
Increasing evidence indicates that cellular metabolism is regulated by mechanical cues from the extracellular environment. Forces transmitted from the microenvironment activate mechanotransduction pathways in the cell, which trigger a cascade of biochemical events that impact cytoskeletal tension, cellular morphology and energy budget available to the cell. Using a nonequilibrium free energy-based theory, we can predict the ATP consumption, contractility, and shape of mesenchymal cancer cells, as well as how cells regulate energy levels dependent on the mechanosensitive metabolic regulator AMPK. The insights from our model can be used to understand the mechanosensitive regulation of metabolism during metastasis and tumor progression, during which cells experience dynamic changes in their microenvironment and metabolic state.
Keyphrases
- induced apoptosis
- stem cells
- cell cycle arrest
- single cell
- breast cancer cells
- cell therapy
- squamous cell carcinoma
- small cell lung cancer
- endoplasmic reticulum stress
- bone marrow
- oxidative stress
- cell death
- poor prognosis
- transcription factor
- signaling pathway
- cell proliferation
- smooth muscle
- pi k akt
- protein kinase