文章：

ID2通过FGFR和JAK-STAT信号通路促进前列腺癌谱系转化

ID2 Promotes Lineage Transition of Prostate Cancer through FGFR and JAK-STAT Signaling

原文发布日期：17 January 2024

DOI: 10.3390/cancers16020392

类型: Article

开放获取: 是

英文摘要：

The use of androgen receptor pathway inhibitors (ARPIs) has led to an increase in the proportion of AR-null prostate cancer, including neuroendocrine prostate cancer (NEPC) and double-negative prostate cancer (DNPC), but the mechanism underlying this lineage transition has not been elucidated. We found that ID2 expression was increased in AR-null prostate cancer. In vitro and in vivo studies confirmed that ID2 promotes PCa malignancy and can confer resistance to enzalutamide in PCa cells. We generated an ID2 UP50 signature, which is capable of determining resistance to enzalutamide and is valuable for predicting patient prognosis. Functional experiments showed that ID2 could activate stemness-associated JAK/STAT and FGFR signaling while inhibiting the AR signaling pathway. Our study indicates a potentially strong association between ID2 and the acquisition of a stem-like phenotype in adenocarcinoma cells, leading to resistance to androgen deprivation therapy (ADT) and next-generation ARPIs in prostate cancer.

摘要翻译： 

雄激素受体通路抑制剂（ARPIs）的使用导致AR阴性前列腺癌（包括神经内分泌前列腺癌[NEPC]和双阴性前列腺癌[DNPC]）比例上升，但这一谱系转化的机制尚未阐明。本研究发现ID2在AR阴性前列腺癌中表达升高。体外及体内实验证实ID2能促进前列腺癌恶性进展，并赋予前列腺癌细胞对恩杂鲁胺的耐药性。我们构建了ID2 UP50特征谱，该特征谱能够判定恩杂鲁胺耐药性，对预测患者预后具有重要价值。功能实验表明ID2可激活干性相关的JAK/STAT和FGFR信号通路，同时抑制AR信号通路。本研究揭示了ID2与腺癌细胞获得干细胞样表型之间存在潜在强关联，这种关联导致前列腺癌对雄激素剥夺疗法（ADT）及新一代ARPIs产生耐药性。

原文链接：

ID2 Promotes Lineage Transition of Prostate Cancer through FGFR and JAK-STAT Signaling