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ST6GAL1-mediated aberrant sialylation promotes prostate cancer progression
Emma Scott1, Emily Archer Goode1, Rebecca Garnham1
1Newcastle University Centre for Cancer, Newcastle University Institute of Biosciences, Newcastle, UK.
The Journal of Pathology
|August 7, 2023
Summary
Aberrant glycosylation, specifically increased alpha2,6 sialylation driven by ST6GAL1, is crucial in prostate cancer progression. Targeting ST6GAL1 offers a new therapeutic strategy for prostate cancer.
Area of Science:
- Oncology
- Glycobiology
- Biochemistry
Background:
- Aberrant glycosylation is a hallmark of cancer, with increased alpha2,6 sialylation of N-glycans frequently observed.
- The sialyltransferase ST6GAL1 drives this modification and is overexpressed in many cancers, yet its role in prostate cancer remains unclear.
Purpose of the Study:
- To investigate the role of ST6GAL1 and alpha2,6 sialylated N-glycans in prostate cancer progression.
- To explore ST6GAL1 as a potential therapeutic target for prostate cancer.
Main Methods:
- Analysis of matched prostate cancer and normal tissue samples from 200 patients.
- MALDI imaging mass spectrometry (MALDI-IMS) to identify specific glycans.
- Monitoring ST6GAL1 levels in plasma samples from over 400 patients.
- In vitro and in vivo studies to assess ST6GAL1 function.
- Evaluation of a sialyltransferase inhibitor (P-3F_AX-Neu5Ac).
Main Results:
- ST6GAL1 is upregulated in prostate cancer tissue and elevated in the plasma of patients with prostate cancer.
- Specific branched alpha2,6 sialylated N-glycans were identified in prostate tumor tissue.
- ST6GAL1 promotes prostate tumor growth and invasion.
- Prostate cancer cells may secrete active ST6GAL1, potentially affecting other cells.
- Alpha2,6 sialylated N-glycans on prostate cancer cells are targetable with P-3F_AX-Neu5Ac.
Conclusions:
- ST6GAL1 and alpha2,6 sialylated N-glycans play a significant role in prostate cancer progression.
- ST6GAL1 represents a potential biomarker and therapeutic target for prostate cancer.
- Inhibiting abnormal sialylation presents a promising avenue for novel prostate cancer therapeutics.
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