MUC1 expression is associated with ST3GAL2 and negatively correlated with the androgen receptor in castration-resistant prostate cancer

• Published in: Glycoconjugate journal Vol. 41; no. 6; pp. 381 - 394
• Main Authors: Nakanishi, Shotaro, Suda, Tetsuji, Tanaka, Kei, Yonamine, Tomoko, Numahata, Kenji, Sugawa, Ai, Oshiro, Takuma, Oshiro, Yoshinori, Saito, Seiichi, Inokuchi, Junichi
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2024; Springer Nature B.V
• Subjects: Androgen receptors; Androgens; Antigens; beta-Galactoside alpha-2,3-Sialyltransferase; Biochemistry; Biomedical and Life Sciences; Castration; Cell Line, Tumor; Developmental stages; Gene Expression Regulation, Neoplastic; Humans; Life Sciences; Male; Malignancy; Metastases; Mucin-1 - genetics; Mucin-1 - metabolism; Pathology; Prostate cancer; Prostate-specific antigen; Prostatic Neoplasms, Castration-Resistant - genetics; Prostatic Neoplasms, Castration-Resistant - metabolism; Prostatic Neoplasms, Castration-Resistant - pathology; Receptors, Androgen - genetics; Receptors, Androgen - metabolism; Sialyltransferases - genetics; Sialyltransferases - metabolism; Stage-Specific Embryonic Antigens - genetics; Stage-Specific Embryonic Antigens - metabolism; Tumor cell lines; Castration-resistant prostate cancer; Stage-specific embryonic antigen-4; MUC1; ST3GAL2; Androgen receptor
• ISSN: 0282-0080; 1573-4986; 1573-4986
• DOI: 10.1007/s10719-024-10173-8

Stage-specific embryonic antigen-4 (SSEA-4) is a developmentally regulated antigen, while expression level of SSEA-4 and / or its synthase ST3GAL2 is associated with prognosis in various malignancies. We have reported a prominent increase of SSEA-4 in castration-resistant prostate cancer (CRPC) and its negative correlation with the androgen receptor (AR). Meanwhile, loss of AR has increased to approximately 30% with the growing use of androgen receptor signaling inhibitor for metastatic CRPC (mCRPC). However, monitoring the progression status of AR-negative prostate cancer is a challenge because it does not produce prostate-specific antigen. Based on the negative relationship of expression between AR and SSEA-4, we hypothesized that a soluble molecule synchronized with SSEA-4 in expression could be a serum marker candidate for AR-negative prostate cancer. Thus, we investigated the molecular background of SSEA-4 expression by ST3GAL2 -knockout in DU145 cells. Here we show that MUC1 is identified as a molecule associated with ST3GAL2 and expressed in AR-negative prostate cancer. A negative correlation of expression between AR and MUC1 was observed in prostate cancer cell lines and CRPC tissues. The average rate of MUC1 expression was nearly 60% in AR-negative prostate cancer cells in CRPC tissues. Level of serum CA15–3 (MUC1) was the highest in mCRPC among various stages and its higher level was associated with faster progression of mCRPC. Our results demonstrate that MUC1 is identified as a ST3GAL2-associated molecule and expressed in AR-negative CRPC cells. Furthermore, level of serum CA15–3 may reflect the progression status of mCRPC.