Abstract
In our previous study, the expression profile of tight junction (TJ) protein claudins (CLDNs) in human osteosarcoma (OS) cells was examined, and the data found the CLDN10 was high expressed in OS cells versus fetal osteoblast cells. Hence, we aim to determine the impacts and the molecular mechanisms of CLDN10 in the metastatic phenotype of OS. The exact expression profiles of CLDN10 and phosphorylated Janus kinase 1 (JAK1) in noncancerous bone tissues and OS tissues were detected via a western blotting and immunohistochemistry method. The OS cells with CLDN10 or JAK1 silencing was established via an RNA interference (RNAi) method, and an osteoblast cell line stably expressing CLDN10 was established via cell transfection. Then, the transfection effects and activation states of JAK1/ signal transducer and activator of transcription1 (Stat1) pathway in OS and osteoblast cells were detected via a western blotting assay. Moreover, the metastatic ability of osteoblast cells and OS cells in vitro were evaluated by means of a cell counting kit-8 (CCK8) assay, colony formation assay in soft agar, transwell assay and wound-healing experiment. The present data revealed that CLDN10 and phospho-JAK1 were up-regulated in OS tissues compared with noncancerous bone tissues. Genetic loss of CLDN10 or JAK1 inhibited the activation of the Stat1 and the malignant phenotype in OS cells. To sum up, our study suggested the CLDN10 enhanced the metastatic phenotype of OS cells via the activation of the JAK1/Stat1 signaling pathway.
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Abbreviations
- CCK8:
-
Cell counting kit-8
- CLDNs:
-
Claudins
- TJ:
-
Tight junction
- IHC:
-
Immunohistochemical analysis
- RNAi:
-
RNA interference
- OS:
-
Osteosarcoma
- JAK1:
-
Janus kinase 1
- Stat1:
-
Signal transducer and activator of transcription1
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We would like to thank American Journal Experts (AJE) for English language editing. This manuscript was edited for English language by American Journal Experts (AJE).
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XZ, XW and AW performed the experiments and analyzed the data. MZ and QL contributed to the conception and design of the study. TL revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Ethics approval (approval no. SDU06384) was approved by the Ethics Committee of Central Hospital of Zibo, Affiliated with Shandong University. This article does not contain any studies with animals performed by any of the authors. The informed consent for participation was obtained from all patients and their parents who participated in this study in an appropriate method.
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Zhang, X., Wang, X., Wang, A. et al. CLDN10 promotes a malignant phenotype of osteosarcoma cells via JAK1/Stat1 signaling. J. Cell Commun. Signal. 13, 395–405 (2019). https://doi.org/10.1007/s12079-019-00509-7
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DOI: https://doi.org/10.1007/s12079-019-00509-7