前列腺癌（PCa）的发展和进展依赖于葡萄糖和脂质代谢的编程，并涉及雄激素受体表达和信号传导的改变。界定支撑这种代谢编程的分子机制对于预后不佳的PCa患者具有直接意义。本研究显示，排序素（sortilin）和辅基蛋白-1（syndecan-1）之间存在动态平衡，能够反映不同的代谢表型。通过组织微阵列技术，我们通过免疫组织化学方法表明，在低级别癌症中高表达排序素，而在高级别疾病中上调表达辅基蛋白-1。在前列腺细胞系的机制研究中发现，在雄激素敏感的LNCaP细胞中，排序素通过调节GLUT1和GLUT4促进葡萄糖代谢，同时通过与蛋白酶颗粒前体生长因子（progranulin）和脂蛋白脂酶（LPL）结合限制脂质代谢。相比之下，在雄激素不敏感的PC3细胞中，辅基蛋白-1上调表达，与LPL相互作用并与β3整合素共定位以促进脂质代谢。此外，缺乏雄激素的LNCaP细胞表达排序素减少，葡萄糖代谢减少，而辅基蛋白-1表达增加，促进与LPL和可能的β3整合素的相互作用。我们报道了一个迄今未被充分重视的PCa分子机制，这可能对疾病进展以及雄激素剥夺治疗如何促进去势抗性PCa具有重要意义。© 2023. Springer Nature Limited.

Prostate cancer (PCa) development and progression relies on the programming of glucose and lipid metabolism, and this involves alterations in androgen receptor expression and signalling. Defining the molecular mechanism that underpins this metabolic programming will have direct significance for patients with PCa who have a poor prognosis. Here we show that there is a dynamic balance between sortilin and syndecan-1, that reports on different metabolic phenotypes. Using tissue microarrays, we demonstrated by immunohistochemistry that sortilin was highly expressed in low-grade cancer, while syndecan-1 was upregulated in high-grade disease. Mechanistic studies in prostate cell lines revealed that in androgen-sensitive LNCaP cells, sortilin enhanced glucose metabolism by regulating GLUT1 and GLUT4, while binding progranulin and lipoprotein lipase (LPL) to limit lipid metabolism. In contrast, in androgen-insensitive PC3 cells, syndecan-1 was upregulated, interacted with LPL and colocalised with β3 integrin to promote lipid metabolism. In addition, androgen-deprived LNCaP cells had decreased expression of sortilin and reduced glucose-metabolism, but increased syndecan-1 expression, facilitating interactions with LPL and possibly β3 integrin. We report a hitherto unappreciated molecular mechanism for PCa, which may have significance for disease progression and how androgen-deprivation therapy might promote castration-resistant PCa.© 2023. Springer Nature Limited.