Mechanics, malignancy, and metastasis: The force journey of a tumor cell
By Sanjay Kumar, Valerie M. Weaver. Cancer Metastasis Review, 2009
954 citations recorded by the source corpus.
A cell undergoes many genetic and epigenetic changes as it transitions to malignancy. Malignant transformation is also accompanied by a progressive loss of tissue homeostasis and perturbations in tissue architecture that ultimately culminates in tumor cell invasion into the parenchyma and metastasis to distant organ sites. Increasingly, cancer biologists have begun to recognize that a critical component of this transformation journey involves marked alterations in the mechanical phenotype of the cell and its surrounding microenvironment. These mechanical differences include modifications in cell and tissue structure, adaptive force-induced changes in the environment, altered processing of micromechanical cues encoded in the extracellular matrix (ECM), and cell-directed remodeling of the extracellular stroma. Here, we review critical steps in this “force journey,” including mechanical contributions to tissue dysplasia, invasion of the ECM, and metastasis. We discuss the biophysical basis of this force journey and present recent advances in the measurement of cellular mechanical properties in vitro and in vivo. We end by describing examples of molecular mechanisms through which tumor cells sense, process and respond to mechanical forces in their environment. While our understanding of the mechanical components of tumor growth, survival and motility remains in its infancy, considerable work has already yielded valuable insight into the molecular basis of force-dependent tumor pathophysiology, which offers new directions in cancer chemotherapeutics.
Subfields: Biomedical Engineering, Cell Biology, Physical and Theoretical Chemistry
View Paper: https://www.semanticscholar.org/paper/b527a21dd90e86dabd79727d0a406d7a36dee81b
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Biomedical Engineering
Citations in the corpus
- Force Triggers YAP Nuclear Entry by Regulating Transport across Nuclear Pores. (2017, neutral): “Thus, targeting the mechanical connection between the nucleus and the cytoskeleton (i.e., the LINC complex) emerges as a potential approach to prevent the adverse effects of tissue stiffening in different diseases (Humphrey et al., 2014; Kumar and Weaver, 2009).”
- Actin dynamics, architecture, and mechanics in cell motility. (2014, background): “A striking example of the link between actin mechanics and pathology, and one that has been receiving increasing attention over the last decade, is cancer metastasis and invasion (165, 204).”
- Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer (2011, neutral): “…in non-ossifying tissues (Sage et al., 1984) during both development and tissue repair, where it mediates ECM remodeling and turnover, and cell-ECM interactions (Engel et al., 1987; Sage et al., 1989; Funk and Sage, 1991; Lane and Sage, 1994; Murphy-Ullrich et al., 1995; Chlenski and Cohn, 2010).”
- The physics of cancer: the role of physical interactions and mechanical forces in metastasis (2011, neutral): “Both in vitro and in vivo , these two microstructural parameters alone greatly enhance cell proliferation and motilit”
- Tumor microenvironment complexity and therapeutic implications at a glance (2020, background): “Also, they may highlight the mechanics of tumor metastasis [20] .”