Matrix Stiffness Contributes to Cancer Progression by Regulating Transcription Factors
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...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-02-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/14/4/1049 |
| _version_ | 1797482068097105920 |
|---|---|
| author | Seiichiro Ishihara Hisashi Haga |
| author_facet | Seiichiro Ishihara Hisashi Haga |
| author_sort | Seiichiro Ishihara |
| collection | DOAJ |
| description | 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 β-catenin and nuclear factor kappa B (NF-κB) 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. |
| first_indexed | 2024-03-09T22:23:02Z |
| format | Article |
| id | doaj.art-4f669b6ac4fe48268be4399d34929762 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T22:23:02Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-4f669b6ac4fe48268be4399d349297622023-11-23T19:10:34ZengMDPI AGCancers2072-66942022-02-01144104910.3390/cancers14041049Matrix Stiffness Contributes to Cancer Progression by Regulating Transcription FactorsSeiichiro Ishihara0Hisashi Haga1Department of Advanced Transdisciplinary Sciences, Faculty of Advanced Life Science, Hokkaido University, N10-W8, Kita-ku, Sapporo 060-0810, JapanDepartment of Advanced Transdisciplinary Sciences, Faculty of Advanced Life Science, Hokkaido University, N10-W8, Kita-ku, Sapporo 060-0810, JapanMatrix 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 β-catenin and nuclear factor kappa B (NF-κB) 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.https://www.mdpi.com/2072-6694/14/4/1049cancerstiffnessextracellular matrixmechanotransductiontranscription factorscancer associated fibroblasts |
| spellingShingle | Seiichiro Ishihara Hisashi Haga Matrix Stiffness Contributes to Cancer Progression by Regulating Transcription Factors Cancers cancer stiffness extracellular matrix mechanotransduction transcription factors cancer associated fibroblasts |
| title | Matrix Stiffness Contributes to Cancer Progression by Regulating Transcription Factors |
| title_full | Matrix Stiffness Contributes to Cancer Progression by Regulating Transcription Factors |
| title_fullStr | Matrix Stiffness Contributes to Cancer Progression by Regulating Transcription Factors |
| title_full_unstemmed | Matrix Stiffness Contributes to Cancer Progression by Regulating Transcription Factors |
| title_short | Matrix Stiffness Contributes to Cancer Progression by Regulating Transcription Factors |
| title_sort | matrix stiffness contributes to cancer progression by regulating transcription factors |
| topic | cancer stiffness extracellular matrix mechanotransduction transcription factors cancer associated fibroblasts |
| url | https://www.mdpi.com/2072-6694/14/4/1049 |
| work_keys_str_mv | AT seiichiroishihara matrixstiffnesscontributestocancerprogressionbyregulatingtranscriptionfactors AT hisashihaga matrixstiffnesscontributestocancerprogressionbyregulatingtranscriptionfactors |