Thymosin beta 4 silencing suppresses proliferation and invasion of non-small cell lung cancer cells by repressing Notch1 activation

Thymosin beta 4 (T beta 4), 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 T beta 4 was highly expressed in certain tumor cells, including lung cancer. However, the exact expression pattern and the role of T beta 4 in non-small cell lung cancer (NSCLC) have not to our knowledge been investigated. In the present study, we confirmed that T beta 4 expression was increased in NSCLC tissues and cell lines. T beta 4 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 T beta 4 gene-silenced cells. Moreover, restoring the Notch1 expression attenuated the function of T beta 4 silencing in NSCLC cells. Taken together, these findings suggest that T beta 4 may play an oncogenic role in NSCLC progression and may be a novel molecular target for anti-NSCLC therapy.