Role of extrinsic physical cues in cancer progression

Abstract

The tumor microenvironment (TME) is a complex system composed of many cell types and an extracellular matrix (ECM). During tumorigenesis, cancer cells constantly interact with cellular components, biochemical cues, and the ECM in the TME, all of which make the environment favorable for cancer growth. Emerging evidence has revealed the importance of substrate elasticity and biomechanical forces in tumor progression and metastasis. However, the mechanisms underlying the cell response to mechanical signals-such as extrinsic mechanical forces and forces generated within the TME-are still relatively unknown. Moreover, having a deeper understanding of the mechanisms by which cancer cells sense mechanical forces and transmit signals to the cytoplasm would substantially help develop effective strategies for cancer treatment. This review provides an overview of biomechanical forces in the TME and the intracellular signaling pathways activated by mechanical cues as well as highlights the role of mechanotransductive pathways through mechanosensors that detect the altering biomechanical forces in the TME. BMB Rep. www.bmbreports.org

Diversity of Intercellular Communication Modes: A Cancer Biology Perspective

“…Biological processes involved in virtually all developmental stages and all physiological processes involve a level of mechanical constraints, whether between cells/tissues, or with ECMs [ 281 , 282 , 283 ]. This is certainly true in the context of tumor progression [ 284 , 285 , 286 , 287 , 288 ]. Cancer progression is associated with defects in mechanotransduction, associated with the ECM, focal adhesions (FAs) and cytoskeletal tensions [ 289 , 290 , 291 ].…”

Emerging paradigms in cancer cell plasticity

“…Metastasis, the primary cause of cancer deaths ( 1 ), occurs through a multistep cascade ( 2 ), beginning with the detachment of cancer cells from the primary tumor, which is followed by local invasion into the surrounding tissue ( 3 ), intravasation into blood or lymphatic vessels ( 4 ), survival of circulating tumor cells (CTCs) ( 5 ), extravasation ( 6 ), colonization of a distant organ ( 7 ), and culminating in the growth of a secondary tumor. Critical cellular traits are acquired at each step of the metastatic cascade as cells transition through distinct states in which they gain new phenotypic and functional features ( 8 , 9 ). While lineage differentiation was once considered unidirectional and irreversible, cell identity is now known to be far more plastic than previously assumed.…”