Here we show that cancer stem cells amount in human lung adenocarcinoma cell line A549 depends on Ecadherin expression. In fact, downregulation of E-cadherin expression enhanced expression of pluripotent genes (c-MYC, NESTIN, OCT3/4 and SOX2) and enriched cell population with the cells possessing the properties of so-called 'cancer stem cells' via activation of Wnt/b-catenin signaling. Repression of Ecadherin also stimulated cell proliferation and migration in vitro, decreased cell amount essential for xenografts formation in nude mice, increased tumors vascularization and growth. On the other hand, Ecadherin upregulation caused opposite effects i.e. diminished the number of cancer stem cells, decreased xenograft vascularization and decelerated tumor growth. Therefore, agents restoring E-cadherin expression may be useful in anticancer therapy.

Introduction. E-cadherin aberrant expression or complete loss is common for a number of human malignant neoplasms, and can be a launching mechanism of an epithelial-mesenchymal transition. Passing through epithelial-mesenchymal transition could in turn promote to the acquisition of so called cancer stem cell phenotype by the transformed cells. The objective of the present study is to reveal the influence of E-cadherin expression level on the amount of cancer stem cells in human colon cancer cell line HCT116. Materials and methods. We have created cell sublines with E-cadherin up- and downregulation and assessed the percentage of cancer stem cells using tumor formation assay, clonogenic assay; we also evaluated profile of cell pluripotency markers. Results and conclusion. We have shown that the proportion of cancer stem cells in human colon adenocarcinoma cell line HCT116 depends on the E-cadherin expression level. E-cadherin expression downregulation results in elevated expression of pluripotency genes and in the increase of proportion of cancer stem cells via activation of Wnt/ß-signalling pathway. E-cadherin upregulation has a reverse effect and decreases the amount of HCT116 cancer stem cells. Thus, E-cadherin expression restoration seems prospective in colorectal anticancer therapy.

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