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

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
• cancer stem cells (CSCs)
• E-cadherin
• tumor progression
• wnt-signaling

Disclosure of potential conflicts of interest

No potential conflicts of interest were disclosed.

Funding

KPB is grateful to the Russian Science Foundation (RSCF), grant No. 14-15-00467 for support.