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STMN2 overexpression promotes cell proliferation and EMT in pancreatic cancer mediated by WNT/β-catenin signaling

Cancer Gene Therapy volume 30, pages 472–480 (2023)Cite this article

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Abstract

STMN2, as a key regulator in microtubule disassembly and dynamics, has recently been shown to participate in cancer development. However, the corresponding role in pancreatic ductal adenocarcinoma (PC), to our knowledge, has not been reported yet. In the current study, we systematically investigate the potential role of STMN2 in the progression of PC in vitro and vivo. Overexpression of STMN2 was prevalently observed in 81 human cases of PC tissues compared with that in the paired adjacent pancreas (54.3% vs 18.5%, P < 0.01), which was positively associated with multiple advanced clinical stages of PC patients (tumor size, T stage, lymph-node metastasis and the poor prognosis). Meanwhile, a close correlation between high STMN2 and cytoplasmic/nuclear β-catenin expression (P = 0.007) was observed in PC tissues and cell lines. STMN2 overexpression induced EMT and cell proliferation in vitro via stimulating EMT-like cellular morphology, cell motility and proliferation, and the change of EMT (Snail1, E-cadherin and Vimentin) and Cyclin D1 signaling. However, XAV939 inhibited STMN2 overexpression-enhanced EMT and proliferation. Conversely, KY19382 reversed STMN2 silencing- inhibited EMT and cell proliferation in vitro. Furthermore, activated STMN2 and β-catenin were co-localized in cytoplasm/nuclear in vitro. β-catenin/TCF-mediated the transcription of STMN2 by the potential binding sites (TTCAAAG). Finally, STMN2 promoted subcutaneous tumor growth following the activation of EMT and Cyclin D1 signaling. STMN2 overexpression promotes the aggressive clinical stage of PC patients and promotes EMT and cell proliferation in vitro and vivo. β-catenin/TCF-mediated the transcription of STMN2.

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Fig. 1: The expression of STMN2 and β-catenin in human PC and adjacent pancreas with the prognosis of PC patients.
Fig. 2: The expression of STMN2 in PC specimens and cell lines and the silencing and overexpressing effect of STMN2 in vitro.
Fig. 3: Cellular morphology (x200 magnification) in vitro.
Fig. 4: STMN2 promoted mobility in vitro mediated by WNT/β-catenin signaling.
Fig. 5: STMN2 promoted cell proliferation in vitro mediated by WNT/β-catenin signaling.
Fig. 6: STMN2 promoted EMT and Cyclin D1 signaling mediated by WNT/β-catenin signaling.
Fig. 7: IF and Chip assays.
Fig. 8: STMN2 promoted subcutaneous tumor size in vivo.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

Thanks for the technical supports from both central laboratory and general laboratory at the First Hospital of China Medical University.

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Authors and Affiliations

  1. Department of Thoracic Surgery, the First Hospital of China Medical University, Shenyang city, Liaoning province, 110001, P. R. China

    Mingrui Shao

  2. Department of Geriatric Surgery, the First Hospital of China Medical University, Shenyang city, Liaoning province, 110001, P. R. China

    Li Wang, Qi Zhang, Tianlong Wang & Shiyang Wang

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Contributions

Conception and design: MRS and SYW; acquisition of data: LW, QZ, and TLW; analysis and interpretation of data: MRS, LW, QZ, and TLW. writing, review, and revision of the manuscript: MRS and SYW.

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Correspondence to Shiyang Wang.

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The authors declare no competing interests.

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The present study was approved by the Ethics Committee of the first hospital of China Medical University. The processing of clinical tissue samples is in strict compliance with the ethical standards of the Declaration of Helsinki. All patients signed written informed consent.

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Shao, M., Wang, L., Zhang, Q. et al. STMN2 overexpression promotes cell proliferation and EMT in pancreatic cancer mediated by WNT/β-catenin signaling. Cancer Gene Ther 30, 472–480 (2023). https://doi.org/10.1038/s41417-022-00568-w

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