Dynamic interplay between sortilin and syndecan-1 contributes to prostate cancer progression

Area of Science:

• Oncology
• Molecular Biology
• Metabolism

Background:

• Prostate cancer (PCa) progression is linked to metabolic reprogramming, involving glucose and lipid pathways.
• Androgen receptor signaling critically influences PCa metabolism.
• Understanding metabolic alterations is vital for improving outcomes in advanced PCa.

Purpose of the Study:

• To elucidate the molecular mechanisms of metabolic reprogramming in prostate cancer.
• To define the roles of sortilin and syndecan-1 in regulating glucose and lipid metabolism in PCa.
• To investigate the dynamic balance between sortilin and syndecan-1 in different PCa grades and conditions.

Main Methods:

• Immunohistochemistry on tissue microarrays to assess sortilin and syndecan-1 expression.
• Mechanistic studies using prostate cancer cell lines (LNCaP and PC3).
• Analysis of protein interactions and cellular localization (e.g., with LPL and β3 integrin).

Main Results:

• Sortilin is highly expressed in low-grade PCa, promoting glucose metabolism and limiting lipid metabolism.
• Syndecan-1 is upregulated in high-grade and androgen-insensitive PCa, promoting lipid metabolism.
• Androgen deprivation in LNCaP cells decreases sortilin and glucose metabolism while increasing syndecan-1 and lipid metabolism.

Conclusions:

• A dynamic balance between sortilin and syndecan-1 defines distinct metabolic phenotypes in prostate cancer.
• This balance is crucial for PCa progression and may underlie the development of castration-resistant PCa.
• Targeting this metabolic regulatory axis could offer new therapeutic strategies for PCa.