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SOX2/SALL4 stemness axis modulates Notch signaling genes to maintain self-renewal capacity of esophageal squamous cell carcinoma

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Abstract

Stemness phenotype is considered as the centerpiece of cancer biology due to its potential in conventional chemo-radiotherapy resistance and tumor recurrence after clinical intervention. This feature in tumor mass belongs to activation of core regulatory stemness factors and different cell signaling pathways in cancer stem cells. We aimed in this study to elucidate contribution of Notch signaling pathway in stemness state of esophageal squamous cell carcinoma (ESCC) through their relevance with stem cell markers SOX2 and SALL4. 50 ESCC tumor and related margin normal tissues were considered and categorized based on SOX2/SALL4 expression pattern, and mRNA levels of Notch signaling genes including ligands, receptors, target genes, and transcriptional coactivator were analyzed in the selected groups using qRT-PCR. Concomitant overexpression of stem cell markers SOX2 and SALL4 in ESCCs upregulated the involved genes in Notch signaling pathway. Upregulation of Notch pathway genes associated with depth of tumor invasion and lymph node metastasis of ESCC. Based on biological function of SOX2 and SALL4 axis in stemness state potential, our results may suggest contribution of Notch signaling pathway in self-renewal capacity of ESCCs, as well as invasion and metastasis of the disease. To the best of our knowledge, this is the first report elucidating the crosstalk between SOX2/SALL4 stemness factors and Notch signaling pathway in cancer research.

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Data availability

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

Abbreviations

CSCs:

Cancer stem cells

EMT:

Epithelial mesenchymal transition

ESCs:

Embryonic stem cells

ESCC:

Esophageal squamous cell carcinoma

iPS:

Induced pluripotent stem

TF:

Transcription factor

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Acknowledgements

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

Funding

Not applicable.

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Authors and Affiliations

  1. Department of Biology, Damghan Branch, Islamic Azad University, Cheshmeh-Ali Boulevard, Sa’dei Square, P.O. Box: 3671639998, Damghan, Islamic Republic of Iran

    Mohammad Mahdi Forghanifard & Paniz Kasebi

  2. Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Mohammad Reza Abbaszadegan

Authors
  1. Mohammad Mahdi Forghanifard
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  2. Paniz Kasebi
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  3. Mohammad Reza Abbaszadegan
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Contributions

MMF designed the study, performed the experiments, analyzed data, drafted and edited the manuscript. PK performed the experiments. MMF and MRA had a critical scientific revision on the manuscript.

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Correspondence to Mohammad Mahdi Forghanifard.

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The authors declare that they have no conflict of interest.

Ethical approval and consent to participate

The study was approved by ethics committee of Mashhad University of Medical Sciences and informed consent was obtained from all individual participants included in the study.

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

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Forghanifard, M.M., Kasebi, P. & Abbaszadegan, M.R. SOX2/SALL4 stemness axis modulates Notch signaling genes to maintain self-renewal capacity of esophageal squamous cell carcinoma. Mol Cell Biochem 476, 921–929 (2021). https://doi.org/10.1007/s11010-020-03956-8

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  • DOI: https://doi.org/10.1007/s11010-020-03956-8

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