Please use this identifier to cite or link to this item:
http://hdl.handle.net/10397/89151
Title: | Fluid shear stress induces EMT of circulating tumor cells via JNK signaling in favor of their survival during hematogenous dissemination | Authors: | Xin, Y Li, K Yang, M Tan, Y |
Issue Date: | 1-Nov-2020 | Source: | International journal of molecular sciences, 1 Nov. 2020, v. 21, no. 21, 8115, p. 1-16 | Abstract: | Tumor cells metastasize to distal organs mainly through hematogenous dissemination, where they experience considerable levels of fluid shear stress. Epithelial–mesenchymal transition (EMT) plays a critical role in tumor metastasis. However, how fluid shear stress influences the EMT phenotype of circulating tumor cells (CTCs) in suspension has not been fully understood. The role of shear-induced EMT in cell survival under blood shear flow remains unclear. This study shows that the majority of breast CTCs underwent apoptosis under shear flow and the surviving cells exhibited mesenchymal phenotype, suggesting that fluid shear stress induces EMT. Mechanistically, fluid shear stress-activated Jun N-terminal kinase (JNK) signaling, inhibition/activation of which suppressed/promoted the EMT phenotype. In particular, shear flow facilitated the JNK-dependent transition of epithelial CTCs into the mesenchymal status and maintained the pre-existing mesenchymal cells. Importantly, the induction of EMT suppressed the pro-apoptosis gene p53 upregulated modulator of apoptosis (PUMA) and enhanced the survival of suspended CTCs in fluid shear stress, which was rescued by overexpressing PUMA or silencing JNK signaling, suggesting that shear-induced EMT promotes CTC survival through PUMA downregulation and JNK activation. Further, the expressions of EMT markers and JUN were correlated with poor patient survival. In summary, our findings have demonstrated that fluid shear stress induces EMT in suspended CTCs via JNK signaling that promotes their survival in shear flow. This study thus unveils a new role of blood shear stress in CTC survival and facilitates the development of novel therapeutics against tumor metastasis. | Keywords: | Circulating tumor cells Epithelial�Mesenchymal transition Fluid shear stress Jnk Metastasis |
Publisher: | Molecular Diversity Preservation International (MDPI) | Journal: | International journal of molecular sciences | ISSN: | 1661-6596 | EISSN: | 1422-0067 | DOI: | 10.3390/ijms21218115 | Rights: | © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). The following publication Xin, Y., Li, K., Yang, M., & Tan, Y. (2020). Fluid shear stress induces emt of circulating tumor cells via jnk signaling in favor of their survival during hematogenous dissemination. International Journal of Molecular Sciences, 21(21), 8115, 1-16 is available at https://dx.doi.org/10.3390/ijms21218115 |
Appears in Collections: | Journal/Magazine Article |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
ijms-21-08115.pdf | 3.48 MB | Adobe PDF | View/Open |
Page views
61
Last Week
0
0
Last month
Citations as of Apr 28, 2024
Downloads
10
Citations as of Apr 28, 2024
SCOPUSTM
Citations
34
Citations as of Apr 4, 2024
WEB OF SCIENCETM
Citations
34
Citations as of May 2, 2024
Google ScholarTM
Check
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.