Abstract
Mechanotransduction is the interpretation of physical cues by cells through mechanosensation mechanisms that elegantly translate mechanical stimuli into biochemical signaling pathways. While mechanical stress and their resulting cellular responses occur in normal physiologic contexts, there are a variety of cancer-associated physical cues present in the tumor microenvironment that are pathological in breast cancer. Mechanistic in vitro data and in vivo evidence currently support three mechanical stressors as mechanical modifiers in breast cancer that will be the focus of this review: stiffness, interstitial fluid pressure, and solid stress. Increases in stiffness, interstitial fluid pressure, and solid stress are thought to promote malignant phenotypes in normal breast epithelial cells, as well as exacerbate malignant phenotypes in breast cancer cells.
Highlights
Introduction to Mechanical SignalingBiophysics is a field of research that endeavors to understand biology from the standpoint of physics, by using physics-based theories and methods, which includes the physical/mechanical properties of cells and surrounding tissue
Mounting observational and experimental evidence supports the presence of a variety of mechanical stimuli in breast cancer that help promote malignancy
One gap in knowledge is the mechanism by which non-tumorigenic breast epithelial cells and breast cancer cells respond and integrate acute mechanical stress
Summary
Biophysics is a field of research that endeavors to understand biology from the standpoint of physics, by using physics-based theories and methods, which includes the physical/mechanical properties of cells and surrounding tissue (e.g., whether they are rigid or pliable). Cells sense changes in the prevailing intracellular and/or extracellular mechanical homeostasis on a molecular level, which initiates intracellular signaling. This translation of physical signals acting on cells to a cellular response via intracellular signaling is known as mechanotransduction. The resulting conversion of mechanical stimuli into electrical and chemical signals (i.e., mechanotransduction) that initiate a cell’s ultimate response will be outlined. The bidirectional interaction between cells and their mechanical microenvironment, known as mechanoreciprocity, is considered These ideas converge on the notion that the cell’s mechanical microenvironment and mechanotransduction signaling are dysregulated in breast cancer, which promotes cancer cell malignant phenotypes and tumor growth.
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