The article discusses the role of mechanical forces in tissue development, homeostasis, and cancer progression. Cells within tissues are continuously exposed to various physical forces, including hydrostatic pressure, shear stress, and compression, which they adapt to by modifying their behavior and remodelling their microenvironment. This adaptation involves both epigenetic chromatin remodeling and direct physical links between the matrix and nucleus that regulate gene expression. The nature of these forces can change in pathologies such as cardiovascular disease and cancer, leading to a loss of mechanoreciprocity, where cells no longer exert reciprocal actomyosin- and cytoskeleton-dependent forces. This loss promotes disease progression, including liver fibrosis, atherosclerosis, and cancer. The article highlights the importance of mechanical forces in normal tissue development and function, such as embryogenesis, tissue-specific development, and adult tissue homeostasis. For example, embryonic stem cells stiffen as they differentiate, and their shape and specification are influenced by the mechanical properties of the tissue microenvironment. In adult tissues, mechanical loading is crucial for maintaining skeletal health and vascular function. The stiffness of tissues and the rheology of cells can profoundly influence cellular behaviors, including differentiation, tissue organization, and cell migration. In cancer, altered mechanical forces contribute to disease progression. Epithelial cancers are characterized by changes in tissue tensional homeostasis, increased cell-generated force, matrix stiffening, and interstitial pressure. These changes can facilitate cancer metastasis and compromise treatment. The article also discusses the relationship between breast density and breast cancer risk, suggesting that dense breasts may be associated with a stiffer breast parenchyma, which could contribute to increased cancer risk. Additionally, the article explores the paradox of increased cancer incidence with age, attributing it to the disproportionate increase in inappropriate post-translational modifications of ECM proteins, leading to matrix stiffening and aberrant matrix crosslinking.The article discusses the role of mechanical forces in tissue development, homeostasis, and cancer progression. Cells within tissues are continuously exposed to various physical forces, including hydrostatic pressure, shear stress, and compression, which they adapt to by modifying their behavior and remodelling their microenvironment. This adaptation involves both epigenetic chromatin remodeling and direct physical links between the matrix and nucleus that regulate gene expression. The nature of these forces can change in pathologies such as cardiovascular disease and cancer, leading to a loss of mechanoreciprocity, where cells no longer exert reciprocal actomyosin- and cytoskeleton-dependent forces. This loss promotes disease progression, including liver fibrosis, atherosclerosis, and cancer. The article highlights the importance of mechanical forces in normal tissue development and function, such as embryogenesis, tissue-specific development, and adult tissue homeostasis. For example, embryonic stem cells stiffen as they differentiate, and their shape and specification are influenced by the mechanical properties of the tissue microenvironment. In adult tissues, mechanical loading is crucial for maintaining skeletal health and vascular function. The stiffness of tissues and the rheology of cells can profoundly influence cellular behaviors, including differentiation, tissue organization, and cell migration. In cancer, altered mechanical forces contribute to disease progression. Epithelial cancers are characterized by changes in tissue tensional homeostasis, increased cell-generated force, matrix stiffening, and interstitial pressure. These changes can facilitate cancer metastasis and compromise treatment. The article also discusses the relationship between breast density and breast cancer risk, suggesting that dense breasts may be associated with a stiffer breast parenchyma, which could contribute to increased cancer risk. Additionally, the article explores the paradox of increased cancer incidence with age, attributing it to the disproportionate increase in inappropriate post-translational modifications of ECM proteins, leading to matrix stiffening and aberrant matrix crosslinking.