The changes in expression of Cadherins enhance metastatic and invasive ability in A431 sub-lines
Date Issued
2007
Date
2007
Author(s)
Tsai, Pei-Hsun
DOI
zh-TW
Abstract
Metastasis is still one of the important areas to study in cancer research fields. Normally, before metastasis, cancer cells exhibit longer shape, and increase their invasion, migration ability by epithelial-mesenchymal transition (EMT). The noticeable properties of EMT are decreasing in E-cadherin expression and cell-cell adhesion. Besides, EMT could induce the degradation of E-cadherin adhesion complex, and translocation of β-catenin into the nucleus as well. The entrance of β-catenin into nucleus will trigger the expression of downstream genes, promote cell proliferation and enhance cell movement. In addition, the decrease of expression of E-cadherin was found to accompany with the increasing expression of N-cadherin, which in turn interacts with many proteins, and switch on signal transduction of cancer cells.
In this study, we use in vitro invasion assay to isolate higher invasive carcinoma cells from A431 parental cells (A431 P). The cells passed through Boyden chamber three times were designed as A431 III. We then used A431 III cells to explore the role of cadherins in cancer metastasis. We observed that the level of E-cadherin showed little change, but the level of β-catenin was slightly increased in the A431 III sub-line as compared to A431 P. In addition, the decrease in interaction of E-cadherin and β-catenin was found in A431 III sub-lines. Moreover, the expression of N-cadherin and FGFR1 was increased in A431 III, and the binding of N-cadherin and FGFR1 was higher than that of A431 P. We further confirmed that the phosphorylation of MAPK/ERK was enhanced and MMP9 secretion was increased in A431 III. The aforementioned results were in agreement with the synergistic pathway of N-cadherin and FGFR-1. On the other hand, we observed that β-catenin didn’t translocate into the nucleus, but switched to bind N-cadherin. This switch may be responsible for stabilization of N-cadherin and induce some signal pathways related to N-cadherin.
In summary, we showed important roles of E-cadherin andβ-catenin in tumor metastasis. The decrease in E-cadherin expression resulted in lose cell-cell adhesion, suggested the importance of E-cadherin as a therapeutic target in cancer metastasis.
Subjects
癌症
轉移
附著蛋白
A431
invasion
EMT
cadherin
β-catenin
FGFR1
SDGs
Type
other