To investigate the potential role of HNF6 in EMT and other relevant cell functions, we examined whether HNF6 can be regulated by TGF-1 during EMT induction. and cell migration, indicating that p53 is required for the functions of HNF6 herein. Moreover, there is a high positive correlation among the expression levels of HNF6, p53, and E-cadherin in human lung cancer cells and tissues. The data suggest that (S)-3-Hydroxyisobutyric acid HNF6 inhibits EMT, cell migration, and invasive growth through a mechanism involving the transcriptional activation of p53. test. A value of < 0.05 was considered statistically significant. *, < 0.05; **, < 0.01. RESULTS Knockdown of HNF6 Induces EMT and Cell Migration Our previous work showed that TGF-1 can induce EMT in human lung cancer cell A549 cells (24, 27). To investigate the potential role of HNF6 in EMT and other relevant cell functions, we examined whether HNF6 can be regulated by TGF-1 during EMT induction. As shown Dnm2 in Fig. 1and and showed a high correlation between the HNF6 and p53 levels. These data further suggest that HNF6 is a regulator for p53 expression and a suppressor of EMT. Analysis of one microarray data set from (S)-3-Hydroxyisobutyric acid NCBI GEO profiles revealed that during colorectal cancer metastasis, HNF6 expression was decreased in lymph node metastasis, as compared with primary (S)-3-Hydroxyisobutyric acid tumor (Fig. 7color staining represents HNF6 and E-cadherin. The statistical data were provided in the table shade stands for the staining of HNF6 and p53. The statistical data were shown in the table is therefore more likely due to its inhibitory effect on EMT and cell proliferation. p53 is an important tumor suppressor gene. It plays important roles in apoptosis, DNA repair, and cell proliferation inhibition, and it has been emerged in recent years a critical inhibitor of EMT. A large number of molecules have been reported to be regulated by p53 (32), and many molecules are shown to control the stability and activity of p53 (33). While much less molecules have been reported to regulate p53 expression through transcriptional regulation of its mRNA level. In this report, we found that HNF6 can positively regulate p53 expression by directly activate its promoter activity, suggesting the roles of HNF6 on EMT, cell migration, cell proliferation, and tumor growth may at least partially through its up-regulation of p53. Besides the roles of p53 mentioned above, stemness inhibition is also an important function of p53 reported in recent years (34, 35). The inhibitory effect of p53 on cell stemness may also be related to its inhibitory effect on EMT because EMT was considered to increase stemness in some circumstances (22, 36). However, as an upstream molecule of p53, whether HNF6 is involved in the regulation of cell stemness remains to be investigated. E-cadherin is one of the most important indicators of epithelial phenotype. In clinical diagnosis, E-cadherin could be used as a prognostic factor in some types of cancers (16, 29). High E-cadherin expression level correlated with less metastatic ability of tumors. HNF6 expression level was highly correlated with E-cadherin not only in lung cancer cell lines but also in human lung cancer tissues, and HNF6 can up-regulate E-cadherin in several lung cancer cell lines. High expression of HNF6 correlated with more epithelial phenotype and less metastatic ability and decreased proliferation. These observations suggest a potential diagnostic value of HNF6 in early clinical cancer diagnosis. In addition, factors that are able to restore or up-regulate the expression of HNF6 may be considered as potential therapeutic candidate molecules in the treatment of some cancers. Acknowledgments We thank Dr. Dang-Sheng Li for helpful and critical comments of this work and Wei-Qiao Ding for certain technical assistance. We also thank other members of the laboratory for many helpful discussions. *This work was supported by grants from.
- Pictures were extracted from five (5) randomly selected optical areas beneath the 10 goal
- One of the most commonly used models for describing individual cell migration in 2D is the persistent random walk (PRW) model,12C14 whose mathematical formulation was originally developed as modified Brownian motion