Inceptor 与前列腺癌进展的标志物相关，调节胰岛素/IGF1 信号和癌细胞迁移。
Inceptor correlates with markers of prostate cancer progression and modulates insulin/IGF1 signaling and cancer cell migration.
机构信息
Institute of Diabetes and Regeneration Research at the Helmholtz Center Munich, Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany; German Center for Diabetes Research (DZD), Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany; Technical University of Munich, School of Medicine, Ismaninger Str. 22, 81675, Munich, Germany.
German Center for Diabetes Research (DZD), Ingolstaedter Landstr. 1, 85764, Neuherberg, Germany; Institute of Diabetes and Metabolic Disease at the Helmholtz Center Munich, Ottfried-Müller-Str. 10, 72076, Tübingen, Germany; Department of Internal Medicine, Division of Endocrinology, Diabetology and Nephrology, University Hospital Tübingen, Ottfried-Müller-Str. 10, 72076, Tübingen, Germany.
出版信息
Mol Metab. 2023 May;71:101706. doi: 10.1016/j.molmet.2023.101706. Epub 2023 Mar 15.
OBJECTIVE
The insulin/insulin-like growth factor 1 (IGF1) pathway is emerging as a crucial component of prostate cancer progression. Therefore, we investigated the role of the novel insulin/IGF1 signaling modulator inceptor in prostate cancer.
METHODS
We analyzed the expression of inceptor in human samples of benign prostate epithelium and prostate cancer. Further, we performed signaling and functional assays using prostate cancer cell lines.
RESULTS
We found that inceptor was expressed in human benign and malignant prostate tissue and its expression positively correlated with various genes of interest, including genes involved in androgen signaling. In vitro, total levels of inceptor were increased upon androgen deprivation and correlated with high levels of androgen receptor in the nucleus. Inceptor overexpression was associated with increased cell migration, altered IGF1R trafficking and higher IGF1R activation.
CONCLUSIONS
Our in vitro results showed that inceptor expression was associated with androgen status, increased migration, and IGF1R signaling. In human samples, inceptor expression was significantly correlated with markers of prostate cancer progression. Taken together, these data provide a basis for investigation of inceptor in the context of prostate cancer.
目的
胰岛素/胰岛素样生长因子 1（IGF1）通路正成为前列腺癌进展的关键组成部分。因此，我们研究了新型胰岛素/IGF1 信号调节剂 inceptor 在前列腺癌中的作用。
方法
我们分析了 inceptor 在人良性前列腺上皮和前列腺癌组织中的表达。此外，我们使用前列腺癌细胞系进行了信号和功能测定。
结果
我们发现 inceptor 在人良性和恶性前列腺组织中表达，其表达与多种感兴趣的基因呈正相关，包括涉及雄激素信号的基因。体外，雄激素剥夺后 inceptor 的总水平增加，并与核内高水平的雄激素受体相关。inceptor 的过表达与细胞迁移增加、IGF1R 转运改变和 IGF1R 激活增加有关。
结论
我们的体外结果表明，inceptor 的表达与雄激素状态、迁移增加和 IGF1R 信号有关。在人样本中，inceptor 的表达与前列腺癌进展的标志物显著相关。综上所述，这些数据为研究 inceptor 在前列腺癌中的作用提供了依据。
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