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Silencing SAPCD2 Represses Proliferation and Lung Metastasis of Fibrosarcoma by Activating Hippo Signaling Pathway
The primary problem associated with fibrosarcoma is its high potential to metastasize to the lung. Aberrant expression of SAPCD2 has been widely reported to be implicated in the progression and metastasis in multiple cancer types. However, the clinical significance and biological roles of SAPCD2 in...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770171/ https://www.ncbi.nlm.nih.gov/pubmed/33384953 http://dx.doi.org/10.3389/fonc.2020.574383 |
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author | Zhu, Bowen Wu, Yanqin Niu, Lizhi Yao, Wang Xue, Miao Wang, Hongyu Yang, Jianyong Li, Jiaping Fan, Wenzhe |
author_facet | Zhu, Bowen Wu, Yanqin Niu, Lizhi Yao, Wang Xue, Miao Wang, Hongyu Yang, Jianyong Li, Jiaping Fan, Wenzhe |
author_sort | Zhu, Bowen |
collection | PubMed |
description | The primary problem associated with fibrosarcoma is its high potential to metastasize to the lung. Aberrant expression of SAPCD2 has been widely reported to be implicated in the progression and metastasis in multiple cancer types. However, the clinical significance and biological roles of SAPCD2 in fibrosarcoma remain unknown. Here, we reported that SAPCD2 expression was markedly elevated in fibrosarcoma tissues, and its expression was differentially upregulated in fibrosarcoma cell lines compared with that in several primary fibroblast cell lines. Kaplan-Meier survival analysis revealed that SAPCD2 overexpression was significantly correlated with early progression and metastasis, and poor prognosis in fibrosarcoma patients. Our results further showed that silencing SAPCD2 inhibited the proliferation and increased the apoptosis of fibrosarcoma cells in vitro. Importantly, silencing SAPCD2 repressed lung metastasis of fibrosarcoma cells in vivo. Mechanistic investigation further demonstrated that silencing SAPCD2 inhibited the proliferation and lung metastasis of fibrosarcoma cells by activating the Hippo signaling pathway, as evidenced by the finding that constitutively active YAP1, YAP1-S127A, significantly reversed the inhibitory effect of SAPCD2 downregulation on the colony formation and anchorage-independent growth capabilities of fibrosarcoma cells, as well as the stimulatory effect on the apoptotic ratio of fibrosarcoma cells. In conclusion, SAPCD2 promotes the proliferation and lung metastasis of fibrosarcoma cells by regulating the activity of Hippo signaling, and this mechanism represents a potential therapeutic target for the treatment of lung metastatic fibrosarcoma. |
format | Online Article Text |
id | pubmed-7770171 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77701712020-12-30 Silencing SAPCD2 Represses Proliferation and Lung Metastasis of Fibrosarcoma by Activating Hippo Signaling Pathway Zhu, Bowen Wu, Yanqin Niu, Lizhi Yao, Wang Xue, Miao Wang, Hongyu Yang, Jianyong Li, Jiaping Fan, Wenzhe Front Oncol Oncology The primary problem associated with fibrosarcoma is its high potential to metastasize to the lung. Aberrant expression of SAPCD2 has been widely reported to be implicated in the progression and metastasis in multiple cancer types. However, the clinical significance and biological roles of SAPCD2 in fibrosarcoma remain unknown. Here, we reported that SAPCD2 expression was markedly elevated in fibrosarcoma tissues, and its expression was differentially upregulated in fibrosarcoma cell lines compared with that in several primary fibroblast cell lines. Kaplan-Meier survival analysis revealed that SAPCD2 overexpression was significantly correlated with early progression and metastasis, and poor prognosis in fibrosarcoma patients. Our results further showed that silencing SAPCD2 inhibited the proliferation and increased the apoptosis of fibrosarcoma cells in vitro. Importantly, silencing SAPCD2 repressed lung metastasis of fibrosarcoma cells in vivo. Mechanistic investigation further demonstrated that silencing SAPCD2 inhibited the proliferation and lung metastasis of fibrosarcoma cells by activating the Hippo signaling pathway, as evidenced by the finding that constitutively active YAP1, YAP1-S127A, significantly reversed the inhibitory effect of SAPCD2 downregulation on the colony formation and anchorage-independent growth capabilities of fibrosarcoma cells, as well as the stimulatory effect on the apoptotic ratio of fibrosarcoma cells. In conclusion, SAPCD2 promotes the proliferation and lung metastasis of fibrosarcoma cells by regulating the activity of Hippo signaling, and this mechanism represents a potential therapeutic target for the treatment of lung metastatic fibrosarcoma. Frontiers Media S.A. 2020-12-15 /pmc/articles/PMC7770171/ /pubmed/33384953 http://dx.doi.org/10.3389/fonc.2020.574383 Text en Copyright © 2020 Zhu, Wu, Niu, Yao, Xue, Wang, Yang, Li and Fan http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Zhu, Bowen Wu, Yanqin Niu, Lizhi Yao, Wang Xue, Miao Wang, Hongyu Yang, Jianyong Li, Jiaping Fan, Wenzhe Silencing SAPCD2 Represses Proliferation and Lung Metastasis of Fibrosarcoma by Activating Hippo Signaling Pathway |
title | Silencing SAPCD2 Represses Proliferation and Lung Metastasis of Fibrosarcoma by Activating Hippo Signaling Pathway |
title_full | Silencing SAPCD2 Represses Proliferation and Lung Metastasis of Fibrosarcoma by Activating Hippo Signaling Pathway |
title_fullStr | Silencing SAPCD2 Represses Proliferation and Lung Metastasis of Fibrosarcoma by Activating Hippo Signaling Pathway |
title_full_unstemmed | Silencing SAPCD2 Represses Proliferation and Lung Metastasis of Fibrosarcoma by Activating Hippo Signaling Pathway |
title_short | Silencing SAPCD2 Represses Proliferation and Lung Metastasis of Fibrosarcoma by Activating Hippo Signaling Pathway |
title_sort | silencing sapcd2 represses proliferation and lung metastasis of fibrosarcoma by activating hippo signaling pathway |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770171/ https://www.ncbi.nlm.nih.gov/pubmed/33384953 http://dx.doi.org/10.3389/fonc.2020.574383 |
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