Dual roles of E‐cadherin in prostate cancer invasion

Abstract

The role(s) of E-cadherin in tumor progression, invasion, and metastasis remains somewhat enigmatic. In order to investigate various aspects of E-cadherin biological activity, particularly in prostate cancer progression, our laboratory cloned unique subpopulations of the heterogeneous DU145 human prostatic carcinoma cell line and characterized their distinct biological functions. The data revealed that the highly invasive, fibroblastic-like subpopulation of DU145 cells (designated DU145-F) expressed less than 0.1-fold of E-cadherin protein when compared to the parental DU145 or the poorly invasive DU145 cells (designated DU145-E). Experimental disruption of E-cadherin function stimulated migration and invasion of DU145-E and other E-cadherin-positive prostate cancer cell lines, but did not affect the fibroblastic-like DU145-F subpopulation. Within the medium of parental DU145 cells, the presence of an 80 kDa E-cadherin fragment was detected. Subsequent functional analyses revealed the stimulatory effect of this fragment on the migratory and invasive capability of E-cadherin-positive cells. These results suggest that E-cadherin plays an important role in regulating the invasive potential of prostate cancer cells through an unique paracrine mechanism.

A Role for the G12 Family of Heterotrimeric G Proteins in Prostate Cancer Invasion

“…Therefore, we were somewhat surprised that G 12 -induced inactivation of E-cadherin was not sufficient to promote invasion of the DU145 cell line. Nevertheless, this result is consistent with a previous report demonstrating that inactivation of E-cadherin on DU145 cells using an antibody to block E-cadherin function resulted in only a minimal increase in cell migration (56). As such, the increase in cell motility resulting from the inactivation of E-cadherin by activated G␣ 12 (⌬244 -249) may not have been sufficient to produce a detectable change in DU145 cell invasion.…”

Epithelial—mesenchymal and mesenchymal—epithelial transitions in carcinoma progression

“…Increased levels of the extracellular domain of N-cadherin have also been detected in the serum of prostate cancer patients (Derycke et al, 2006). Importantly, the functional importance of decreased E-cadherin levels has also been demonstrated in prostate cancer cells with its inverse correlation with cellular motility and protease expression (Chunthapong et al, 2004). These changes in epithelial and mesenchymal markers and the loss of prostatic glandular architecture are consistent with the general dedifferentiated phenotype of aggressive prostate cancer cells, although decisive evidence for EMT remains elusive.…”

Expression and Subcellular Localization of E-Cadherin, .ALPHA.-Catenin, and .BETA.-Catenin in 8 Feline Mammary Tumor Cell Lines

“…α-Catenin serves as a bridge between E-cadherin and β-catenin, both of which connect with the microfilament cytoskeleton [20]. Disruption of normal cell-cell adhesion by alterations in cadherin-catenin molecules may contribute to enhanced migration and proliferation of tumor cells, thereby leading to invasion and metastasis [13].In human and experimental animal models, loss of E-cadherin expression was reported to cause cell migration or metastasis of tumor cells in breast cancers [11], gastric cancers [2], colorectal cancers [9], and prostate cancers [4]. Along with abnormalities of E-cadherin, the relationship between the disruption of the cell adhesion system and α-and β-catenin expressions was also reported in these cancers [7,8,17].…”

“…In human and experimental animal models, loss of E-cadherin expression was reported to cause cell migration or metastasis of tumor cells in breast cancers [11], gastric cancers [2], colorectal cancers [9], and prostate cancers [4]. Along with abnormalities of E-cadherin, the relationship between the disruption of the cell adhesion system and α-and β-catenin expressions was also reported in these cancers [7,8,17].…”