title: Thymosin beta 4 silencing suppresses proliferation and invasion of non-small cell lung cancer cells by repressing Notch1 activation.
abstract: Thymosin beta 4 (Tβ4), a pleiotropic actin-sequestering polypeptide that is involved in wound healing and developmental processes, has been reported to be strongly associated with tumorigenesis. A recent tissue microarray analysis showed that Tβ4 was highly expressed in certain tumor cells, including lung cancer. However, the exact expression pattern and the role of Tβ4 in non-small cell lung cancer (NSCLC) have not to our knowledge been investigated. In the present study, we confirmed that Tβ4 expression was increased in NSCLC tissues and cell lines. Tβ4 gene silencing in A549 and H1299 cells inhibited cell proliferation, migration, and invasion in vitro and decreased tumor growth in vivo Mechanistic investigations revealed a significant decrease in Notch1 activation in Tβ4 gene-silenced cells. Moreover, restoring the Notch1 expression attenuated the function of Tβ4 silencing in NSCLC cells. Taken together, these findings suggest that Tβ4 may play an oncogenic role in NSCLC progression and may be a novel molecular target for anti-NSCLC therapy.
authors: Department of Thoracic Surgery, Shanghai Pulmonary Hospital of Tongji University, Shanghai 200433, China.
authors: Dayu
authors: D
authors: Huang
authors: Department of Cardiothoracic Surgery, Huashan Hospital of Fudan University, Shanghai 200040, China.
authors: Shaohua
authors: S
authors: Wang
authors: Department of Thoracic Surgery, Shanghai Pulmonary Hospital of Tongji University, Shanghai 200433, China.
authors: An
authors: A
authors: Wang
authors: Department of Cardiothoracic Surgery, Huashan Hospital of Fudan University, Shanghai 200040, China chenxiaofeng0724@sina.com zhanghuijunhp@163.com.
authors: Xiaofeng
authors: X
authors: Chen
authors: Department of Cardiothoracic Surgery, Huashan Hospital of Fudan University, Shanghai 200040, China chenxiaofeng0724@sina.com zhanghuijunhp@163.com.
authors: Huijun
authors: H
authors: Zhang
mesh_terms: D000072283:A549 Cells; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000235:genetics; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction; D013947:Thymosin / Q000037:antagonists & inhibitors* / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays; D000099201:Thymosin beta(4)
chemical_list: D051881:Receptor, Notch1; D013947:Thymosin; D000099201:Thymosin beta(4); C497761:NOTCH1 protein, human
keywords: NSCLC; Notch1; Tβ4; invasion; migration; proliferation