Cytoskeletal alteration modulates cancer cell invasion through RhoA-YAP signaling in stromal fibroblasts.
Cancer-associated fibroblasts(CAFs) participate in carcinogenesis through interaction with cancer cells. This study aimed to investigate the mechanism of cytoskeletal alteration of CAFs and its role in invasion of oral squamous cell carcinoma(OSCC).Immortalized normal fibroblasts(hTERT-hNOFs) co-cul...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0214553 |
| _version_ | 1819003852705234944 |
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| author | Do Kyeong Kim Eun Kyoung Kim Da-Woon Jung Jin Kim |
| author_facet | Do Kyeong Kim Eun Kyoung Kim Da-Woon Jung Jin Kim |
| author_sort | Do Kyeong Kim |
| collection | DOAJ |
| description | Cancer-associated fibroblasts(CAFs) participate in carcinogenesis through interaction with cancer cells. This study aimed to investigate the mechanism of cytoskeletal alteration of CAFs and its role in invasion of oral squamous cell carcinoma(OSCC).Immortalized normal fibroblasts(hTERT-hNOFs) co-cultured with OSCC cells showed myofibroblastic and senescent phenotypes like CAFs. Thus, this study substituted hTERT-hNOFs for CAFs. Next, the cytoskeletal alteration and its molecular mechanism were investigated in hTERT-hNOFs co-cultured with OSCC. As results, we found that RhoA regulated cytoskeletal organization in fibroblasts surrounding OSCC cells. Furthermore, as a downstream transcriptional factor of RhoA, YAP was mainly localized in the nucleus of hTERT-hNOFs co-cultured with OSCC. Consequently, we examined whether nuclear YAP localization of fibroblasts could influence cancer progression. YAPS127A fibroblasts manifesting nuclear localization of YAP induced cytoskeletal alteration and increased gel contractility and matrix stiffness, and thereby enhances the invasiveness of OSCC cells. In conclusion, the modification of tumor microenvironment, such as cytoskeletal change and matrix remodeling via RhoA-YAP in CAFs, modulates OSCC invasion. These understandings will provide the development of novel approaches for CAFs-based cancer therapy. |
| first_indexed | 2024-12-20T23:27:35Z |
| format | Article |
| id | doaj.art-ee7ae3d0a5794e5fbd9175357f73d2ca |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T23:27:35Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ee7ae3d0a5794e5fbd9175357f73d2ca2022-12-21T19:23:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01143e021455310.1371/journal.pone.0214553Cytoskeletal alteration modulates cancer cell invasion through RhoA-YAP signaling in stromal fibroblasts.Do Kyeong KimEun Kyoung KimDa-Woon JungJin KimCancer-associated fibroblasts(CAFs) participate in carcinogenesis through interaction with cancer cells. This study aimed to investigate the mechanism of cytoskeletal alteration of CAFs and its role in invasion of oral squamous cell carcinoma(OSCC).Immortalized normal fibroblasts(hTERT-hNOFs) co-cultured with OSCC cells showed myofibroblastic and senescent phenotypes like CAFs. Thus, this study substituted hTERT-hNOFs for CAFs. Next, the cytoskeletal alteration and its molecular mechanism were investigated in hTERT-hNOFs co-cultured with OSCC. As results, we found that RhoA regulated cytoskeletal organization in fibroblasts surrounding OSCC cells. Furthermore, as a downstream transcriptional factor of RhoA, YAP was mainly localized in the nucleus of hTERT-hNOFs co-cultured with OSCC. Consequently, we examined whether nuclear YAP localization of fibroblasts could influence cancer progression. YAPS127A fibroblasts manifesting nuclear localization of YAP induced cytoskeletal alteration and increased gel contractility and matrix stiffness, and thereby enhances the invasiveness of OSCC cells. In conclusion, the modification of tumor microenvironment, such as cytoskeletal change and matrix remodeling via RhoA-YAP in CAFs, modulates OSCC invasion. These understandings will provide the development of novel approaches for CAFs-based cancer therapy.https://doi.org/10.1371/journal.pone.0214553 |
| spellingShingle | Do Kyeong Kim Eun Kyoung Kim Da-Woon Jung Jin Kim Cytoskeletal alteration modulates cancer cell invasion through RhoA-YAP signaling in stromal fibroblasts. PLoS ONE |
| title | Cytoskeletal alteration modulates cancer cell invasion through RhoA-YAP signaling in stromal fibroblasts. |
| title_full | Cytoskeletal alteration modulates cancer cell invasion through RhoA-YAP signaling in stromal fibroblasts. |
| title_fullStr | Cytoskeletal alteration modulates cancer cell invasion through RhoA-YAP signaling in stromal fibroblasts. |
| title_full_unstemmed | Cytoskeletal alteration modulates cancer cell invasion through RhoA-YAP signaling in stromal fibroblasts. |
| title_short | Cytoskeletal alteration modulates cancer cell invasion through RhoA-YAP signaling in stromal fibroblasts. |
| title_sort | cytoskeletal alteration modulates cancer cell invasion through rhoa yap signaling in stromal fibroblasts |
| url | https://doi.org/10.1371/journal.pone.0214553 |
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