YAP/TAZ Related BioMechano Signal Transduction and Cancer Metastasis

Abstract

Mechanoreciprocity refers to a cell’s ability to maintain tensional homeostasis in response to various types of forces. Physical forces are continually being exerted upon cells of various tissue types, even those considered static, such as the brain. Through mechanoreceptors, cells sense and subsequently respond to these stimuli. These forces and their respective cellular responses are prevalent in regulating everything from embryogenic tissue-specific differentiation, programmed cell death, and disease progression, the last of which being the subject of extensive attention. Abnormal mechanical remodeling of cells can provide clues as to the pathological status of tissues. This becomes particularly important in cancer cells, where cellular stiffness has been recently accepted as a novel biomarker for cancer metastasis. Several studies have also elucidated the importance of cell stiffness in cancer metastasis, with data highlighting that a reversal of tumor stiffness has the capacity to revert the metastatic properties of cancer. In this review, we summarize our current understanding of extracellular matrix (ECM) homeostasis, which plays a prominent role in tissue mechanics. We also describe pathological disruption of the ECM, and the subsequent implications toward cancer and cancer metastasis. In addition, we highlight the most novel approaches toward understanding the mechanisms which generate pathogenic cell stiffness and provide potential new strategies which have the capacity to advance our understanding of one of human-kinds’ most clinically significant medical pathologies. These new strategies include video-based techniques for structural dynamics, which have shown great potential for identifying full-field, high-resolution modal properties, in this case, as a novel application.

Cancer Metastasis: The Role of the Extracellular Matrix and the Heparan Sulfate Proteoglycan Perlecan

“…Hydration of tumor tissue is strongly influenced by the presence of specific glycosaminoglycans (GAGs) within the tissue, due to their anionic structure and their ability to attract water. As hydration increases, increased intratumoral hydrostatic pressure rises and alters the biomechanical properties of the tissue which is known to be crucial to invasiveness (29,30). Perfusion of nutrients, growth and chemotactic factors are also affected leading to changes in cancer cell invasion (31).…”

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

“…Among typical YAP/TAZ targets are several secretory factors, including amphiregulin, connective tissue growth factor (CTGF) and cysteine-rich angiogenic inducer 61 (CYR61), which are important in stromal interactions and niche formation of cancer metastasis [18][19][20][21][22].There is ample and rapidly growing literature on the mechanisms of YAP/TAZ regulation, particularly by the Hippo signaling pathway, which prohibits organ overgrowth through the regulation of cell proliferation and cell survival during normal development. Recent excellent and comprehensive reviews summarize this wealth of published information from different angles: from a protein structural perspective [23,24]; from the angle of tissue mechanics, microenvironment and cytoskeleton interactions [25][26][27]; from the aspect of DNA-binding protein partners of YAP/TAZ [28,29] and in the context of normal development [30]; specific cancers (i.e., of the breast [31], lung [32] liver [33], prostate [34], pancreas [35] and various pediatric cancers [36]) and other chronic and neurodegenerative diseases [37,38].The adaptation to microenvironments of different tissue architecture plays a particularly important role in bone cancers which tend to metastasize through the hematogenous route and home primarily to bone and lungs, which are organs of completely different stiffness, extracellular matrix composition and oxygen supply. It is therefore not unexpected that the YAP/TAZ signaling pathway is prominently involved in bone cancer pathogenesis and metastatic spread.…”

“…There is ample and rapidly growing literature on the mechanisms of YAP/TAZ regulation, particularly by the Hippo signaling pathway, which prohibits organ overgrowth through the regulation of cell proliferation and cell survival during normal development. Recent excellent and comprehensive reviews summarize this wealth of published information from different angles: from a protein structural perspective [23,24]; from the angle of tissue mechanics, microenvironment and cytoskeleton interactions [25][26][27]; from the aspect of DNA-binding protein partners of YAP/TAZ [28,29] and in the context of normal development [30]; specific cancers (i.e., of the breast [31], lung [32] liver [33], prostate [34], pancreas [35] and various pediatric cancers [36]) and other chronic and neurodegenerative diseases [37,38].…”

Regulation and mechanism of YAP/TAZ in the mechanical microenvironment of stem cells (Review)

“…For example, YAP/TAZ has been identified in the mechanical mechanics micro-environment response ( 3 , 62 ), but the specific details of the mechanism have yet to be studied. Therefore, further study of YAP/TAZ regulation is required to increase understanding of the role of force in the pathogenesis of certain diseases and the role of trauma repair processes in mediating these mechanisms, which may lead to novel effective treatment strategies ( 128 , 129 ). This also applies to tissue engineering, gene therapy, stem cell regeneration medicine and space and aerospace medicine research.…”