NFAT promotes carcinoma invasive migration through glypican-6

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Original languageEnglish
Pages (from-to)157-166
Journal / PublicationBiochemical Journal
Issue number1
Publication statusPublished - 15 Nov 2011
Externally publishedYes


Invasive migration of carcinoma cells is a prerequisite for the metastatic dissemination of solid tumours. Numerous mechanisms control the ability of cancer cells to acquire a motile and invasive phenotype, and subsequently degrade and invade the basement membrane. Several genes that are up-regulated in breast carcinoma are responsible for mediating the metastatic cascade. Recent studies have revealed that the NFAT (nuclear factor of activated T-cells) is a transcription factor that is highly expressed in aggressive breast cancer cells and tissues, and mediates invasion through transcriptional induction of pro-invasion and migration genes. In the present paper we demonstrate that NFAT promotes breast carcinoma invasion through induction of GPC (glypican) 6, a cell-surface glycoprotein. NFAT transcriptionally regulates GPC6 induction in breast cancer cells and binds to three regulatory elements in the GPC6 proximal promoter. Expression of GPC6 in response to NFAT signalling promotes invasive migration, whereas GPC6 silencing with shRNA (small-hairpin RNA) potently blocks this phenotype. The mechanism by which GPC6 promotes invasive migration involves inhibition of canonical β-catenin andWnt signalling, and up-regulation of noncanonical Wnt5A signalling leading to the activation of JNK (c-Jun N-terminal kinase) and p38MAPK(mitogen-activated protein kinase). Thus GPC6 is a novel NFAT target gene in breast cancer cells that promotes invasive migration through Wnt5A signalling. © 2011 The Author(s).

Research Area(s)

  • Breast cancer, Cancer invasion, Glypican, Nuclear factor of activated t-cells (NFAT), Transcription factor

Citation Format(s)

NFAT promotes carcinoma invasive migration through glypican-6. / Yiu, Gary K.; Kaunisto, Aura; Chin, Y. Rebecca; Toker, Alex.

In: Biochemical Journal, Vol. 440, No. 1, 15.11.2011, p. 157-166.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review