Department of Molecular Medicine, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
Department of Microbiology & Immunology, Pusan National University School of Medicine, Yangsan 50612, Republic of Korea.
Biomolecules. 2024 Aug 13;14(8):997. doi: 10.3390/biom14080997.
Clinically, prostate cancer is infamous for its histological and molecular heterogeneity, which causes great challenges to pinpoint therapy and pharmaceutical development. To overcome these difficulties, researchers are focusing on modulating tumor microenvironment and immune responses in addition to genetic alteration and epigenetic regulation. Here, we aimed to identify potential biomarkers or modulators of prostate cancer by investigating genes specifically altered in prostate cancer cells treated with established anti-cancer agents. Glycerol kinase 1 (GK1) is phosphotransferase encoded on the X chromosome, is associated with the synthesis of triglycerides and glycerophospholipids, and has been mainly studied for X-linked metabolic disorder GK deficiency (GKD). Interestingly, our DNA microarray analysis showed that several anti-cancer agents highly induced the expression of GK1, especially GK1a and GK1b isoforms, in human prostate cancer PC-3 cells. To elucidate the relationship between GK1 and cancer cell death, a human GK1b-specific expression vector was constructed and transfected into the PC-3 cells. Surprisingly, GK1b overexpression dramatically reduced cell viability and significantly accelerated apoptotic cell death. These findings suggest that GK1b may serve as a promising modulator and biomarker of cell death in prostate cancer, offering potential avenues for therapeutic intervention.
临床上,前列腺癌以其组织学和分子异质性而臭名昭著,这给精确定位治疗和药物开发带来了巨大挑战。为了克服这些困难,研究人员除了关注遗传改变和表观遗传调控外,还专注于调节肿瘤微环境和免疫反应。在这里,我们旨在通过研究在经过既定抗癌药物处理的前列腺癌细胞中特异性改变的基因,来鉴定前列腺癌的潜在生物标志物或调节剂。甘油激酶 1(GK1)是一种编码在 X 染色体上的磷酸转移酶,与甘油三酯和甘油磷脂的合成有关,主要用于研究 X 连锁代谢疾病 GK 缺乏症(GKD)。有趣的是,我们的 DNA 微阵列分析显示,几种抗癌药物在人前列腺癌细胞 PC-3 中高度诱导 GK1 的表达,特别是 GK1a 和 GK1b 同工型。为了阐明 GK1 与癌细胞死亡之间的关系,构建了人 GK1b 特异性表达载体并转染到 PC-3 细胞中。令人惊讶的是,GK1b 的过表达显著降低了细胞活力,并显著加速了细胞凋亡。这些发现表明,GK1b 可能作为前列腺癌细胞死亡的有前途的调节剂和生物标志物,为治疗干预提供了潜在途径。