E-Cadherin repression increases amount of cancer stem cells in human A549 lung adenocarcinoma and stimulates tumor growth

Cell Cycle. 2016;15(8):1084-92. doi: 10.1080/15384101.2016.1156268.

Abstract

Here we show that cancer stem cells amount in human lung adenocarcinoma cell line A549 depends on E-cadherin 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/β-catenin signaling. Repression of E-cadherin 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, E-cadherin 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.

Keywords: B-catenin; E-cadherin; cancer stem cells (CSCs); tumor progression; wnt-signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Animals
  • Antigens, CD
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Cell Count
  • Cell Proliferation
  • Cell Shape
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Mice, Nude
  • Models, Biological
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • RNA, Small Interfering / metabolism
  • Repressor Proteins / metabolism*
  • Wnt Signaling Pathway / genetics

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • RNA, Small Interfering
  • Repressor Proteins