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PTK7 promotes the malignant properties of cancer stem-like cells in esophageal squamous cell lines

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Abstract

This study was performed to investigate the role of PTK7 in esophageal squamous cell carcinoma (ESCC) stem-like cells (CSCs). PTK7 expression in ESCCs identified by RT-qPCR, and CSC-like cells were isolated from populations of NEC and TE-1 cells. The CSC-like cells were verified by flow cytometric analyses performed using CD34 and CD133 antibodies, and RT-qPCR and western blot assays were used to examine the self-renewal capability of CSC-like cells. CSC-like cells treated with PTK7 siRNA or a P53-specific inhibitor (PFTα) were analyzed for their sphere formation capacity and their apoptosis and migration/invasion capabilities by sphere formation, flow cytometry, and transwell assay, respectively. Their levels of P53, MKK3, and cleaved caspase 3 expression were examined by western blot analysis. Our results revealed that a majority of the isolated CSC-like cells were CD34+/CD133+ double positive cells. Nango, Sox2, and OCT4 were dramatically increased in the separated CSC-like cells, which had the pluripotency and self-renewal properties of stem cells. Additional, PTK7 was dramatically upregulated in the ESCC tissues and CSC-like cells. An investigation of the function of CSC-like cells revealed that knockdown of PTK7 reduced their sphere formation, promoted apoptosis, and suppressed their migration and invasion abilities, all of which could be significantly reversed by PFTα. Mechanistic studies showed that PFTα could attenuate the upregulation of P53, MKK3, and cleaved caspase 3 expression that was induced by PTK7 knockdown in CSC-like cells. PTK7 increased the malignant behaviors of CSC-like cells derived from ESCC cells by regulating p53. Therefore, this study suggests PTK7 as an underlying target for therapy against ESCC.

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Abbreviations

CSC:

Cancer stem cell

ESCC:

Esophageal squamous cell carcinoma

OCT4:

POU class 5 homeobox 1

PTK7:

Protein tyrosine kinase 7

SOX2:

SRY-box transcription factor 2

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Acknowledgements

This work was supported by the National Science Foundation for Distinguished Young Scholars of China (No. 81903026).

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Authors and Affiliations

  1. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, 1# of Youyi Rd, Yuzhong District, Chongqing, 400016, People’s Republic of China

    Jun Bie & Ziwei Wang

  2. Department of Oncology, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, 637000, People’s Republic of China

    Jun Bie, Xin Hu, Mi Yang, Xianwei Shi & Xinping Zhang

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  1. Jun Bie
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  2. Xin Hu
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  3. Mi Yang
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Contributions

JB and ZWW contributed to the research design. JB performed the experiments. JB and XH collected the data and analyzed the data. MY and XWS validated the data and analysis. XPZ contributed to results description and data visualization. JB drafted the manuscript and ZWW revised the manuscript. All authors approved the manuscript before submission.

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Correspondence to Ziwei Wang.

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The authors have no commercial or other associations that might pose a conflict of interest.

Ethical approval

This study was approved by the Ethics Committee of The First Affiliated Hospital of Chongqing Medical University. All study procedures were performed in accordance with the ethical principles stated in the Declaration of Helsinki.

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Bie, J., Hu, X., Yang, M. et al. PTK7 promotes the malignant properties of cancer stem-like cells in esophageal squamous cell lines. Human Cell 33, 356–365 (2020). https://doi.org/10.1007/s13577-019-00309-6

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