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STAT3 mediates RCP-induced cancer cell invasion through the NF-κB/Slug/MT1-MMP signaling cascade

Abstract

Rab coupling protein (RCP) has been known to induce cancer invasion and metastasis, and STAT3 is one of major oncogenic factors. In the present study, we identify the critical role of STAT3 in RCP-induced cancer cell invasion. Immunohistochemical data of ovarian cancer tissues presented that levels of RCP expression are closely correlated with those of phospho-STAT3 (p-STAT3). In addition, ovarian cancer patients with high expression of both RCP and p-STAT3 had significantly lower progress-free and overall survival rates compared to those with low either RCP or p-STAT3 expression. Mechanistically, RCP induced STAT3 phosphorylation in both ovarian and breast cancer cells. Silencing or pharmacological inhibition of STAT3 significantly inhibited RCP-induced cancer cell invasion. In addition, we provide evidence that the β1 integrin/EGFR axis is important for RCP-induced STAT3 phosphorylation. Furthermore, STAT3 activated NF-κB for Slug expression that in turn upregulated MT1-MMP expression for cancer cell invasion. Collectively, our present data demonstrate that STAT3 is located downstream of the β1 integrin/EGFR axis and induces Slug and MT1-MMP expression for cancer cell invasion.

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Acknowledgements

This work is supported by grants from the Basic Science Research Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science, and Technology (NRF-2017R1E1A1A01074091 and 2022R1A2C1004019).

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Correspondence to Hoi Young Lee.

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Cho, S.J., Jeong, B.Y., Song, Y.S. et al. STAT3 mediates RCP-induced cancer cell invasion through the NF-κB/Slug/MT1-MMP signaling cascade. Arch. Pharm. Res. 45, 460–474 (2022). https://doi.org/10.1007/s12272-022-01396-0

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  • DOI: https://doi.org/10.1007/s12272-022-01396-0

Keywords

  • Rab coupling protein
  • STAT3
  • Cancer cell invasion
  • Slug
  • MT1-MMP