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Stemness state regulators SALL4 and SOX2 are involved in progression and invasiveness of esophageal squamous cell carcinoma

Medical Oncology volume 31, Article number: 922 (2014) Cite this article

Abstract

Cancer stem cells, as a subgroup of tumor cells, resemble critical properties of embryonic stem cells (ESCs) such as self-renewal and maintenance of stemness state. SALL4 and SOX2 are two main transcription factors involving in maintenance of pluripotency, self-renewal and cell fate decision in ESCs. In this study, we aimed to elucidate the expression levels of these important transcription factors in esophageal squamous cell carcinoma (ESCC) and to reveal their probable roles in maintenance and progression of the disease. The expression level of SALL4 and SOX2 was analyzed in fresh tumoral tissues in comparison with distant tumor-free tissues of 50 ESCC patients by relative comparative real-time PCR. SALL4 and SOX2 were overexpressed in 64 and 32 % of tumor samples, respectively, in significant correlation with each other (p = 0.028). There was a significantly inverse correlation between low level of SALL4 expression and metastasis of tumor cells into the lymph nodes (p = 0.035). Furthermore, co-overexpression of the genes was significantly correlated with the depth of tumor invasion (p = 0.045) and metastasis to the lymph nodes (p = 0.049). SALL4 and SOX2 are co-overexpressed in ESCC and have a significant correlation with invasion and metastasis of the disease. To the best of our knowledge, this is the first report of SALL4 clinical relevance in ESCC to date. The clinical consequences of SALL4–SOX2 association suggest a possible functional interaction between these factors in regulation of ESCC maintenance and aggressiveness and introduce these regulators of stemness state as potentially interesting therapeutic targets to bring new opportunities for onco-therapeutic modalities.

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Acknowledgments

The authors gratefully acknowledge the colleagues from the departments of surgery and pathology at Omid Hospital and also the colleagues at the Division of Human Genetics for their help in gathering and preparing the tissue specimens.

Conflict of interest

The authors declare that they have no conflict of interests.

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Authors and Affiliations

  1. Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Islamic Republic of Iran

    Mohammad Mahdi Forghanifard

  2. Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad University of Medical Sciences, Bu-Ali Square, Mashhad, 9196773117, Islamic Republic of Iran

    Sima Ardalan Khales, Afsaneh Javdani-Mallak, Abolfazl Rad & Mohammad Reza Abbaszadegan

  3. Department of Biochemistry and Nutrition, Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, Islamic Republic of Iran

    Abolfazl Rad

  4. Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Islamic Republic of Iran

    Moein Farshchian

  5. Medical Genetics Research Center, Medical School, Mashhad University of Medical Sciences, Mashhad, Islamic Republic of Iran

    Mohammad Reza Abbaszadegan

Authors
  1. Mohammad Mahdi Forghanifard
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  2. Sima Ardalan Khales
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  3. Afsaneh Javdani-Mallak
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  6. Mohammad Reza Abbaszadegan
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Correspondence to Mohammad Reza Abbaszadegan.

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Forghanifard, M.M., Ardalan Khales, S., Javdani-Mallak, A. et al. Stemness state regulators SALL4 and SOX2 are involved in progression and invasiveness of esophageal squamous cell carcinoma. Med Oncol 31, 922 (2014). https://doi.org/10.1007/s12032-014-0922-7

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  • DOI: https://doi.org/10.1007/s12032-014-0922-7

Keywords

  • SALL4
  • SOX2
  • Stemness state
  • ESCC
  • Cancer stem cell