Feng Jie, Yu Sheng-Yuan, Li Chu-Zhong, Li Zhen-Ye, Zhang Ya-Zhuo
Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Beijing Institute for Brain Disorders Brain Tumor Center, China National Clinical Research Center for Neurological Diseases, Capital Medical University, Beijing, 100050, China.
Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Beijing Institute for Brain Disorders Brain Tumor Center, China National Clinical Research Center for Neurological Diseases, Capital Medical University, Beijing, 100050, China; Department of Neurosurgery, Shandong Provincial Hospital, Shandong University, Jinan, 250021, China.
Mol Cell Endocrinol. 2016 Nov 15;436:195-203. doi: 10.1016/j.mce.2016.07.025. Epub 2016 Jul 25.
Non-functioning pituitary adenomas (NFPAs) are a highly heterogeneous group, but few studies have explored the invasion mechanism of specific subtypes of NFPAs. The objective of this study was to investigate the differential molecular expression patterns and the critical biological signaling pathways involved in the invasion of pituitary null cell adenomas (PNCAs) through integrative proteomics and transcriptomics. A total of 1160 genes and 283 proteins were found to be differentially expressed in invasive and non-invasive PNCAs. The differentially expressed molecules related to invasion were enriched in 15 canonical signaling pathways, 15 clusters of diseases or biological functions and 5 upstream molecules. Among them, the majority of the differentially expressed molecules were found to be involved in transport of molecule, migration of cells and cell movement. Notably, IL-6 was a significantly activated upstream regulator, and the IL6R/JAK2/STAT3 cascade was found to play a critical role in acute phase response signaling, which was the most significant canonical signaling pathway. Furthermore, we validated the overexpression of IL-6R, JAK2, STAT3, p-STAT3 and MMP9 in invasive PNCAs. Our data suggest that overactivation of the IL-6R/JAK2/STAT3/MMP9 pathway is critical for the invasion of PNCAs.
无功能垂体腺瘤（NFPAs）是一个高度异质性的群体，但很少有研究探讨NFPAs特定亚型的侵袭机制。本研究的目的是通过整合蛋白质组学和转录组学，研究垂体无细胞腺瘤（PNCAs）侵袭过程中差异分子表达模式及关键生物学信号通路。共发现1160个基因和283种蛋白质在侵袭性和非侵袭性PNCAs中差异表达。与侵袭相关的差异表达分子富集于15条经典信号通路、15个疾病或生物学功能簇以及5个上游分子中。其中，大多数差异表达分子参与分子转运、细胞迁移和细胞运动。值得注意的是，IL-6是一个显著激活的上游调节因子，且发现IL6R/JAK2/STAT3级联在急性期反应信号通路中起关键作用，这是最显著的经典信号通路。此外，我们验证了IL-６R、JAK2、STAT3、p-STAT3和MMP9在侵袭性PNCAs中的过表达。我们的数据表明，IL-6R/JAK2/STAT3/MMP9通路的过度激活对PNCAs的侵袭至关重要。
