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Updated: Jun 2, 2026

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
α-Mannosidase 2C1 attenuates PTEN function in prostate cancer cells
Lizhi He1, Catherine Fan, Anil Kapoor
1Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada L8N 4A6.
Abstract:
PTEN dephosphorylates the 3-position phosphate of phosphatidylinositol 3,4,5 triphosphate (PIP(3)), 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 PIP(3) phosphatase activity. These findings show that MAN2C1 function as a PTEN-negative regulator in PC cells.
Insights
Alpha-mannosidase 2C1 (MAN2C1) inhibits phosphatase and tensin homolog (PTEN) function in prostate cancer cells. MAN2C1 promotes tumor growth by activating AKT signaling, highlighting its role as a PTEN-negative regulator.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- PTEN dephosphorylates phosphatidylinositol 3,4,5 triphosphate (PIP(3)), inhibiting AKT activation.
- PTEN dysfunction is crucial in tumorigenesis, but mechanisms remain unclear.
Purpose of the Study:
- To investigate the role of alpha-mannosidase 2C1 (MAN2C1) in regulating PTEN function in prostate cancer (PC).
Main Methods:
- Investigated MAN2C1's effect on PTEN in PC cells and patient samples.
- Analyzed PTEN and AKT activation in relation to MAN2C1 expression.
- Examined MAN2C1-PTEN interaction and its impact on PIP(3) phosphatase activity.
Main Results:
- MAN2C1 inhibits PTEN function and activates AKT in PC cells.
- MAN2C1 overexpression correlates with PTEN-positive tumors and PC recurrence.
- MAN2C1 binds PTEN, impairing its PIP(3) phosphatase activity.
Conclusions:
- MAN2C1 acts as a PTEN-negative regulator in prostate cancer.
- MAN2C1 promotes tumor growth by inhibiting PTEN and activating AKT.
- MAN2C1 is a potential therapeutic target in PTEN-positive prostate cancer.
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