HAX-1 Promotes the Chemoresistance, Invasion, and Tumorigenicity of Esophageal Squamous Carcinoma Cells (Retracted article. See vol. 64, pg. 2368, 2019)
HAX-1 Promotes the Chemoresistance, Invasion, and Tumorigenicity of Esophageal Squamous Carcinoma Cells (Retracted article. See vol. 64, pg. 2368, 2019)
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DOI：
10.1007/s10620-012-2108-5
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发表时间：
2012-07-01
影响因子：
3.1
通讯作者：
Dong, Zi-ming
中科院分区：
文献类型：
--
作者：
Sun, Sa-jia;Feng, Long;Dong, Zi-ming
HAX-1是一种抗凋亡因子，调节DNA pol β的表达。有趣的是，DNA聚合酶pol β在食管鳞状细胞癌（ESCC）中过表达。为探讨HAX-1在食管鳞癌耐药、侵袭和致瘤性中的作用，本研究采用慢病毒介导的过表达或敲低HAX-1的方法，建立了不同水平表达HAX-1的食管鳞癌细胞系EC 9706。使用异种移植裸小鼠模型在体外和体内表征了这些工程细胞的生物学行为。RT-PCR和免疫组化检测HAX-1和pol β在肿瘤组织中的表达，HAX-1过表达促进细胞增殖，增加细胞对顺铂的耐药性，增加细胞侵袭能力，沿着pol β表达，抑制细胞凋亡。相反，HAX-1敲低抑制EC 9706细胞的恶性表型。异种移植裸鼠模型证明，HAX-1过表达或耗竭分别导致体内肿瘤生长增加或减少。HAX-1与pol β在食管鳞癌组织中的表达呈正相关，HAX-1促进食管鳞癌的增殖、耐药、侵袭和致瘤性，并与pol β表达增加相关。HAX-1可能成为克服食管鳞癌耐药和转移的潜在靶点。
HAX-1 is an anti-apoptotic factor and regulates the expression of DNA pol beta. Interestingly, DNA polymerase pol beta 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 beta 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 beta 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 beta 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 beta expression. HAX-1 may represent a potential target to overcome the resistance and metastasis of ESCC.