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Hokkaido University Collection of Scholarly and Academic Papers >
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Matrix Stiffness Contributes to Cancer Progression by Regulating Transcription Factors
This item is licensed under:Creative Commons Attribution 4.0 International
| Title: | Matrix Stiffness Contributes to Cancer Progression by Regulating Transcription Factors |
| Authors: | Ishihara, Seiichiro Browse this author →KAKEN DB | | Haga, Hisashi Browse this author →KAKEN DB |
| Keywords: | cancer | | stiffness | | extracellular matrix | | mechanotransduction | | transcription factors | | cancer associated fibroblasts | | YAP | | TAZ | | collagen | | contraction | | crosslinking |
| Issue Date: | Feb-2022 |
| Publisher: | MDPI |
| Journal Title: | Cancers |
| Volume: | 14 |
| Issue: | 4 |
| Start Page: | 1049 |
| Publisher DOI: | 10.3390/cancers14041049 |
| Abstract: | Simple Summary Matrix stiffness is recognized as a critical factor in cancer progression. Recent studies have shown that matrix stiffening is caused by the accumulation, contraction, and crosslinking of the extracellular matrix by cancer and stromal cells. Cancer and stromal cells respond to matrix stiffness, which determines the phenotypes of these cells. In addition, matrix stiffness activates and/or inactivates specific transcription factors in cancer and stromal cells to regulate cancer progression. In this review, we discuss the mechanisms of cancer stiffening and progression that are regulated by transcription factors responding to matrix stiffness. Matrix stiffness is critical for the progression of various types of cancers. In solid cancers such as mammary and pancreatic cancers, tumors often contain abnormally stiff tissues, mainly caused by stiff extracellular matrices due to accumulation, contraction, and crosslinking. Stiff extracellular matrices trigger mechanotransduction, the conversion of mechanical cues such as stiffness of the matrix to biochemical signaling in the cells, and as a result determine the cellular phenotypes of cancer and stromal cells in tumors. Transcription factors are key molecules for these processes, as they respond to matrix stiffness and are crucial for cellular behaviors. The Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) is one of the most studied transcription factors that is regulated by matrix stiffness. The YAP/TAZ are activated by a stiff matrix and promotes malignant phenotypes in cancer and stromal cells, including cancer-associated fibroblasts. In addition, other transcription factors such as beta-catenin and nuclear factor kappa B (NF-kappa B) also play key roles in mechanotransduction in cancer tissues. In this review, the mechanisms of stiffening cancer tissues are introduced, and the transcription factors regulated by matrix stiffness in cancer and stromal cells and their roles in cancer progression are shown. |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/85063 |
| Appears in Collections: | 生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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