α-Mannosidase 2C1 attenuates PTEN function in prostate cancer cells

Lizhi He, Catherine Fan, Anil Kapoor, Alistair J. Ingram, Adrian P. Rybak, Richard C. Austin, Jeffery Dickhout, Jean-Claude Cutz, James Scholey and Damu Tang ()
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Lizhi He: McMaster University
Catherine Fan: McMaster University
Anil Kapoor: McMaster University
Alistair J. Ingram: McMaster University
Adrian P. Rybak: McMaster University
Richard C. Austin: McMaster University
Jeffery Dickhout: McMaster University
Jean-Claude Cutz: McMaster University
James Scholey: University of Toronto
Damu Tang: McMaster University

Nature Communications, 2011, vol. 2, issue 1, 1-11

Abstract: Abstract PTEN dephosphorylates the 3-position phosphate of phosphatidylinositol 3,4,5 triphosphate (PIP3), thereby inhibiting AKT activation. Although attenuation of PTEN function has a major role in tumourigenesis, the underlying mechanisms remain unclear. Here we show that α-mannosidase 2C1 (MAN2C1) inhibits PTEN function in prostate cancer (PC) cells and is associated with a reduction in PTEN function in primary PC. MAN2C1 activates AKT and promotes the formation of PTEN-positive DU145 cell-derived xenograft tumours by imparing endogenous PTEN function. In 659 PC patients who were examined, ∼60% of tumours were PTEN positive with elevated AKT activation. Of these, 80% display MAN2C1 overexpression that co-localizes with PTEN. Increases in MAN2C1 were detected only in PTEN-positive prostatic intraepithelial neoplasia and carcinomas, and showed a significant association with PC recurrence only in patients with PTEN-positive PCs. Mechanistically, MAN2C1 binds PTEN thereby inhibiting its PIP3 phosphatase activity. These findings show that MAN2C1 function as a PTEN-negative regulator in PC cells.

Date: 2011
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DOI: 10.1038/ncomms1309

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