Acquired expression of NFATc1 downregulates e-cadherin and promotes cancer cell invasion

Tsukasa Oikawa, Atsuko Nakamura, Nobuyuki Onishi, Taketo Yamada, Koichi Matsuo, Hideyuki Saya

研究成果: Article査読

23 被引用数 (Scopus)

抄録

NFATc1 is a transcription factor that regulates T-cell development, osteoclastogenesis, and macrophage function. Given that T cells, osteoclasts, and macrophages in the tumor microenvironment are thought to modulate tumor progression, tumor cells may acquire NFATc1 expression through fusion with these NFATc1- expressing normal cells. We here revealed that a small proportion of tumor cells in human carcinoma specimens expressed NFATc1. To investigate the consequences of NFATc1 acquisition by tumor cells, we established A549 and MCF7 cell lines expressing a constitutively active form of NFATc1 (NFATc1CA) in an inducible manner. The expression of NFATc1CA promoted cancer cell invasion in association with changes in cell morphology. Analysis of gene expression andRNAinterference experiments revealed that NFATc1CA suppressed E-cadherin expression by upregulating the transcriptional repressors Snail and Zeb1 in a manner independent of TGF-b signaling. Induced expression of NFATc1CA also downregulated E-cadherin expression and increased invasive activity in tumor xenografts in vivo. Our results thus suggest that the acquisition of NFATc1 expression contributes to tumor progression.

本文言語English
ページ(範囲)5100-5109
ページ数10
ジャーナルCancer Research
73
16
DOI
出版ステータスPublished - 2013 8月 15

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究

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