title: Loss of E-cadherin promotes prostate cancer metastasis via upregulation of metastasis-associated gene 1 expression.
abstract: E-cadherin is a key cell-to-cell adhesion molecule associated with the invasion and metastasis of tumor cells; however, the molecular mechanisms are not entirely understood. In this study, we investigated whether downregulation of E-cadherin by E-cadherin-specific small intefering RNA (siRNA) was able to promote malignant phenotypes of prostate cancer cells through upregulating the metastasis-associated gene 1 (MTA1) in vitro. The expression levels of E-cadherin in human paired prostate adenocarcinoma cell lines, PC-3M-2B4 (2B4) and PC-3M-1E8 (1E8), were investigated using western blot analysis. The alteration of malignant phenotypes associated with decreasing E-cadherin expression were assessed in 2B4 cells using wound-healing assays, solid-phase adhesion assays, invasion assays and cytoskeletal staining. The expression of E-cadherin and MTA1 in normal, localized and metastatic prostate cancer cells was analyzed using immunohistochemistry. Downregulation of E-cadherin using an RNA interference approach led to the upregulation of MTA1 expression, decreased tumor cell adhesion ability as well as enhanced cell mobility, invasion and cellular polarity compared with the controls (P<0.05). E-cadherin regulated MTA1 in a time-dependent manner. The correlation between E-cadherin and MTA1 was inversed in the prostate cancer group (P<0.05; r(s)=-0.434). The data suggest that E-cadherin plays an important role in prostate cancer metastasis, which is likely to be due to the regulation of MTA1 expression. E-cadherin may combine with MTA1 and alter the malignant phenotype of prostate cancer cells. A combined testing strategy for detecting MTA1 and E-cadherin may be sufficient for selecting high-risk patients with metastasis. Therefore, E-cadherin and MTA1 may be potential powerful factors for the treatment of various types of cancer.
authors.affiliation: Cancer Biology Medical Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030;
authors.forename: Liangsheng
authors.initials: L
authors.lastname: Fan
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
authors.forename: Xi
authors.initials: X
authors.lastname: Xia
authors.forename: Yumei
authors.initials: Y
authors.lastname: Rao
authors.forename: Xiangyi
authors.initials: X
authors.lastname: Ma
authors.forename: Ding
authors.initials: D
authors.lastname: Ma
authors.forename: Peng
authors.initials: P
authors.lastname: Wu
authors.forename: Gang
authors.initials: G
authors.lastname: Chen