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The inhibition of Panc1 cancer cells invasion by hAMSCs secretome through suppression of tyrosine phosphorylation of SGK223 (at Y411 site), c-Src (at Y416, Y530 sites), AKT activity, and JAK1/Stat3 signaling

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Abstract

SGK223 is a scaffolding protein involving in the oncogenic tyrosine kinase signaling. SGK223 was phosphorylated at Y411 by c-Src and in response to the Epidermal growth factor receptor (EGFR). Tyrosine phosphorylated SGK223 at Y411 enables to interact with CSK resulting up regulation of c-Src activity and promotion of the cell migration. Human amniotic mesenchymal stromal cells (hAMSCs) are a population of multipotent cells that it was considered to be as a potential platform in cancer therapy. Herein, we employed a co-culture system to clarify the effects of hAMSCs secretome through tyrosine phosphorylation of c-Src, SGK223, AKT activity, and JAK1/Stat3 signaling in Panc1 pancreatic cancer cells. By using the 0.4 μm pore sized transwell membranes, both cell lines were firstly co-cultured for 72 h. Next, c-Src activity (tyrosine phosphorylation levels at Y530 and Y416), tyrosine phosphorylation level of SGK223 (at Y411), AKT activity, and JAK1/Stat3 signaling in Panc1 cells after treatment with hAMSCs were evaluated. Our results showed that hAMSCs have the inhibitory effects on Panc1 pancreatic cancer cells invasion and it suggests that the suppression of c-Src activity, SGK223 expression, AKT activity, and JAK1/Stat3 signaling may be as critical targets in pancreatic cancer therapy.

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Data availability

The datasets used or analyzed in the present study are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran

    Fatemeh Safari & Nasim Shafiee Nejad

  2. Department of Biology, University Campus 2, University of Guilan, Rasht, Iran

    Azadeh Aghaei Nejad

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  1. Fatemeh Safari
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  2. Nasim Shafiee Nejad
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  3. Azadeh Aghaei Nejad
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F.S. designed the research, performed the experiments, and wrote the paper. F.S., N.S.N., and A.A.N. analyzed data.

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Correspondence to Fatemeh Safari.

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Safari, F., Shafiee Nejad, N. & Aghaei Nejad, A. The inhibition of Panc1 cancer cells invasion by hAMSCs secretome through suppression of tyrosine phosphorylation of SGK223 (at Y411 site), c-Src (at Y416, Y530 sites), AKT activity, and JAK1/Stat3 signaling. Med Oncol 39, 28 (2022). https://doi.org/10.1007/s12032-022-01649-4

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  • DOI: https://doi.org/10.1007/s12032-022-01649-4

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