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The implications and mechanisms of the extra-nuclear nucleolin in the esophageal squamous cell carcinomas

Medical Oncology volume 32, Article number: 45 (2015) Cite this article

Abstract

In recent decades, the multi-functional protein nucleolin (NCL) has been reported to express outside the nucleus of many cancer cells. However, the expression and role of the extra-nuclear NCL in esophageal squamous cell carcinoma (ESCC) were not well characterized. Here, NCL was detected by immunohistochemistry and Western blotting in 60 ESCC tissues. Further, the associations of NCL, EGFR, CXCR4 and Ki67 were analyzed by in vitro assays. Our results showed that NCL expression in all 40 cases of ESCC tissues with metastasis was extensively located in the nucleus, cytoplasm and cell membrane (extra-nucleus), while NCL expression in all 20 cases of ESCC without metastasis was merely limited into the nucleus (intra-nucleus).The extra-nuclear NCL expression was positively correlated with the expression of EGFR, CXCR4 and Ki67 and serves as an independent prognostic factor for ESCC patients. In vitro, NCL siRNA (si-NCL) efficaciously affected the expression of EGF or SDF-1-induced p-AKT, p-ERK and Ki67. Also, NCL siRNA inhibited the capacity of migration and invasion of ECA109 cells. In conclusions, our study suggests that NCL is implicated in the initiation and transduction of EGFR and CXCR4 signaling and further up-regulates Ki67 expression to modulate the biological behaviors of ESCC. Clinically, the extra-nuclear NCL expression can be used as an important indicator to determine metastasis and predict the prognosis, which help develop new therapeutic strategies against ESCC.

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Acknowledgments

We greatly thank other members in our laboratory for valuable suggestions and writing.

Conflict of interest

None.

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Author notes

    Affiliations

    1. Nan Fang Hospital, Southern Medical University, Guangzhou, China

      Jiafeng Qi & Nanbo Liu

    2. Department of Cardiothoracic Surgery, The First Affiliated Hospital of Jiamusi University, Jiamusi, China

      Jiafeng Qi, Yutong Xing & Gang Zhou

    3. Department of Pediatrics, The First Affiliated Hospital of Jiamusi University, Jiamusi, China

      Huiling Li

    4. Department of Orthopedics, The First Hospital of Inner Mongolia Hohhot, Hohhot, China

      Yao Wu

    5. Department of Emergency, The First Hospital of Inner Mongolia Hohhot, Hohhot, China

      Yuanhang Liu

    6. Department of Infection, The First Hospital of Inner Mongolia Hohhot, Hohhot, China

      Wenxia Chen

    7. Department of General Surgery, Hainan General Hospital, Hainan, China

      Jie Yue

    8. Department of Thoracic Surgery, People’s Hospital of Inner Mongolia Medical University, Hohhot, China

      Bater Han

    9. Department of Thoracic Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China

      Shirong Kang

    10. Department of Cardiothoracic Surgery, Nan Fang Hospital, Southern Medical University, No. 1838 The North of The Guangzhou Road, Baiyun District, Guangzhou, 510515, China

      Xu Wu

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    1. Jiafeng Qi
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    2. Huiling Li
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    7. Yuanhang Liu
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    10. Bater Han
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    11. Shirong Kang
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    12. Xu Wu
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    Corresponding author

    Correspondence to Xu Wu.

    Additional information

    Jiafeng Qi, Huiling Li and Nanbo Liu have contributed equally to this work as the co-first author.

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    Cite this article

    Qi, J., Li, H., Liu, N. et al. The implications and mechanisms of the extra-nuclear nucleolin in the esophageal squamous cell carcinomas. Med Oncol 32, 45 (2015). https://doi.org/10.1007/s12032-015-0484-3

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    • DOI: https://doi.org/10.1007/s12032-015-0484-3

    Keywords

    • Nucleolin
    • EGFR
    • CXCR4
    • Ki67
    • ESCC