XB130 as an Independent Prognostic Factor in Human Esophageal Squamous Cell Carcinoma |
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Authors: | Atsushi Shiozaki MD PhD Toshiyuki Kosuga MD Daisuke Ichikawa MD PhD Shuhei Komatsu MD PhD Hitoshi Fujiwara MD PhD Kazuma Okamoto MD PhD Daisuke Iitaka MD Shingo Nakashima MD Hiroki Shimizu MD Takeshi Ishimoto MD Maki Kitagawa MD Yoshito Nakou MD Mitsuo Kishimoto MD PhD Mingyao Liu MD Eigo Otsuji MD PhD |
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Institution: | 1. Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan 2. Department of Pathology, Kyoto Prefectural University of Medicine, Kyoto, Japan 3. Latner Thoracic Surgery Research Laboratories, University Health Network Toronto General Research Institute, Toronto, ON, Canada 4. Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
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Abstract: | Background Adaptor proteins, with multimodular structures, can participate in the regulation of various cellular functions. A novel adaptor protein XB130 has been implicated as a substrate and regulator of tyrosine kinase-mediated signaling and in controlling cell proliferation and apoptosis in thyroid and lung cancer cells. However, its expression and role in gastrointestinal cancer have not been investigated. We sought to determine the role of XB130 in cell cycle progression of esophageal squamous cell carcinoma (ESCC) cells and to examine its expression and effects on the prognosis of patients with ESCC. Methods Expression of XB130 in human ESCC cell lines was analyzed by Western blot testing and immunofluorescent staining. Knockdown experiments with XB130 small interfering RNA (siRNA) were conducted, and the effect on cell cycle progression was analyzed. Immunohistochemistry of XB130 for 52 primary tumor samples obtained from patients with ESCC undergoing esophagectomy was performed. Results XB130 was highly expressed in TE2, TE5, and TE9 cells. In these cells, knockdown of XB130 with siRNA inhibited G1–S phase progression and increased the expression of p21, the cyclin-dependent kinase inhibitor. Immunohistochemistry showed that 71.2 % of the patients expressed XB130 in the nuclei and/or cytoplasm of the ESCC cells. Further, nuclear expression of XB130 was an independent prognostic factor of postoperative survival. Conclusions These observations suggest that the expression of XB130 in ESCC cells may affect cell cycle progression and impact prognosis of patients with ESCC. A deeper understanding of XB130 as a mediator and/or biomarker in ESCC is needed. |
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