Cytoskeletal alteration modulates cancer cell invasion through RhoA-YAP signaling in stromal fibroblasts

Do Kyeong Kim, Eun Kyoung Kim, Da Woon Jung, Jin Kim

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Article numbere0214553
JournalPloS one
Volume14
Issue number3
DOIs
Publication statusPublished - 2019 Mar 1

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cell invasion
Fibroblasts
fibroblasts
Squamous Cell Carcinoma
squamous cell carcinoma
Cells
mouth
neoplasms
Neoplasms
Tumor Microenvironment
neoplasm cells
Cancer-Associated Fibroblasts
Carcinogenesis
Gels
Stiffness matrix
cells
Epithelial Cells
Phenotype
carcinogenesis
Tumors

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Kim, Do Kyeong ; Kim, Eun Kyoung ; Jung, Da Woon ; Kim, Jin. / Cytoskeletal alteration modulates cancer cell invasion through RhoA-YAP signaling in stromal fibroblasts. In: PloS one. 2019 ; Vol. 14, No. 3.
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abstract = "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.",
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Cytoskeletal alteration modulates cancer cell invasion through RhoA-YAP signaling in stromal fibroblasts. / Kim, Do Kyeong; Kim, Eun Kyoung; Jung, Da Woon; Kim, Jin.

In: PloS one, Vol. 14, No. 3, e0214553, 01.03.2019.

Research output: Contribution to journalArticle

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