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TWIST1 correlates with Notch signaling pathway to develop esophageal squamous cell carcinoma

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Abstract

Notch signaling pathway mediates different biological processes including stem cell self-renewal, progenitor cell fate decision, and terminal differentiation. TWIST1 plays a key role in tumor development and metastasis through inducing epithelial-mesenchymal transition (EMT). Expression of the core transcriptional complex of Notch pathway and its target genes, as well as TWIST1 overexpression, are closely related to the aggressive clinicopathological variables of esophageal squamous cell carcinoma (ESCC). Here we aimed to functionally elucidate probable crosstalk between TWIST1 and Notch pathway in ESCCs. Correlation between TWIST1 and Notch target genes was analyzed in 50 ESCCs and corresponding normal tissues. Using retroviral system, enforced expression of TWIST1 was established in ESCC line KYSE-30 cells and expression of Notch signaling genes was assessed. Significant correlation between TWIST1 and HEY1/HEY2 expression was found in different pathological variable of ESCC poor prognosis. Induced expression of TWIST1 in KYSE-30 cells caused a noteworthy increase of Notch pathway genes expression revealing regulatory role of TWIST1 on Notch signaling genes in the cells. Based on existed correlations between expression of TWIST1 and Notch pathway genes in different pathological features of ESCC patients, as well as KYSE-30 cell line, we may extrapolate that TWIST1 is involved in aggressiveness of the disease through regulation of Notch signaling genes. To the best of knowledge, this is the first report describing the impact of TWIST1 on Notch cascade genes in ESCC.

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All raw data are available on case of reasonable request from corresponding author.

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Acknowledgement

The authors gratefully acknowledge the colleagues at the Division of Human Genetics, Avicenna Research Institute, MUMS, for preparing ESCC tissue specimens.

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Author notes

  1. Yasaman Fahim and Mozhgan Yousefi have contributed equally in this study.

Authors and Affiliations

  1. Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Yasaman Fahim & Mohammad Hossein Izadpanah

  2. Department of Biology, Damghan Branch, Islamic Azad University, Cheshmeh-Ali Boulevard, Sa’dei Square, Damghan, Iran

    Mozhgan Yousefi & Mohammad Mahdi Forghanifard

Authors
  1. Yasaman Fahim
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  2. Mozhgan Yousefi
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  3. Mohammad Hossein Izadpanah
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  4. Mohammad Mahdi Forghanifard
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Contributions

YF, MY and MHI performed the experiments. YF drafted the manuscript. MMF designed the study, analyzed data, edited and revised the manuscript, and had a critical scientific revision on the manuscript.

Corresponding author

Correspondence to Mohammad Mahdi Forghanifard.

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The authors declare that they have no conflict of interest.

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The study was approved by ethics committee of Mashhad University of Medical Sciences.

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Written informed consent was obtained from the patient for publication of their individual details and accompanying images in this manuscript. All authors declared their consent for publication.

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Fahim, Y., Yousefi, M., Izadpanah, M.H. et al. TWIST1 correlates with Notch signaling pathway to develop esophageal squamous cell carcinoma. Mol Cell Biochem 474, 181–188 (2020). https://doi.org/10.1007/s11010-020-03843-2

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  • DOI: https://doi.org/10.1007/s11010-020-03843-2

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