HAX-1 promotes the chemoresistance, invasion, and tumorigenicity of esophageal squamous carcinoma cells

• Published in: Digestive diseases and sciences 2012-07, Vol.57 (7), p.1838-1846
• Main Authors: Sun, Sa-jia, Feng, Long, Zhao, Guo-qiang, Dong, Zi-ming
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - drug effects; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - physiology; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - physiopathology; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell Survival - physiology; Cell Transformation, Neoplastic - pathology; Cisplatin - pharmacology; Cisplatin - therapeutic use; Disease Models, Animal; Drug Resistance, Neoplasm - physiology; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - pathology; Esophageal Neoplasms - physiopathology; Female; HEK293 Cells; Humans; In Vitro Techniques; Mice; Mice, Nude; Neoplasm Invasiveness - physiopathology; RNA, Small Interfering - pharmacology; Transplantation, Heterologous
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-012-2108-5

HAX-1 is an anti-apoptotic factor and regulates the expression of DNA pol β. Interestingly, DNA polymerase pol β is overexpressed in esophageal squamous cell carcinoma (ESCC). However, the functional role of HAX-1 in ESCC remains unclear. To investigate the role of HAX-1 in chemoresistance, invasion, and tumorigenicity of ESCC. Lentivirus-mediated overexpression or knockdown of HAX-1 was employed to establish ESCC EC9706 cell lines that expressed HAX-1 at different levels. The biological behaviors of these engineered cells were characterized in vitro and in vivo using a xenograft nude mice model. In addition, HAX-1 and pol β expression in the tumor tissues was detected by RT-PCR and immunohistochemistry. HAX-1 overexpression promoted cell proliferation and resistance against cisplatin, increased cell invasion and suppressed apoptosis along with increased pol β expression. Conversely, HAX-1 knockdown inhibited the malignant phenotypes of EC9706 cells. The xenograft nude mice model demonstrated that HAX-1 overexpression or depletion led to increased or decreased tumor growth in vivo, respectively. Furthermore, a positive correlation of HAX-1 and pol β expression in the tumor tissues was observed. HAX-1 promotes the proliferation, chemoresistance, invasion, and tumorigenicity of ESCC, and this is correlated with increased poly β expression. HAX-1 may represent a potential target to overcome the resistance and metastasis of ESCC.