Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Eur J Endocrinol. 2022 May 12;187(1):49-64. doi: 10.1530/EJE-21-1183.
Provide insights into the defective POMC processing and invasive behavior in silent pituitary corticotroph tumors.
Single-cell RNAseq was used to compare the cellular makeup and transcriptome of silent and active corticotroph tumors.
A series of transcripts related to hormone processing peptidases and genes involved in the structural organization of secretory vesicles were reduced in silent compared to active corticotroph tumors. Most relevant to their invasive behavior, silent corticotroph tumors exhibited several features of epithelial-to-mesenchymal transition, with increased expression of mesenchymal genes along with the loss of transcripts that regulate hormonal biogenesis and secretion. Silent corticotroph tumor vascular smooth muscle cell and pericyte stromal cell populations also exhibited plasticity in their mesenchymal features.
Our findings provide novel insights into the mechanisms of impaired POMC processing and invasion in silent corticotroph tumors and suggest that a common transcriptional reprogramming mechanism simultaneously impairs POMC processing and activates tumor invasion.
深入了解沉默性垂体促肾上腺皮质细胞瘤中 POMC 加工缺陷和侵袭行为的机制。
利用单细胞 RNA 测序比较沉默性和活性促肾上腺皮质细胞瘤的细胞组成和转录组。
与活性促肾上腺皮质细胞瘤相比，沉默性促肾上腺皮质细胞瘤中与激素加工肽酶相关的一系列转录本和参与分泌囊泡结构组织的基因减少。与它们的侵袭行为最相关的是，沉默性促肾上腺皮质细胞瘤表现出上皮-间充质转化的几个特征，间充质基因表达增加，同时调节激素生物发生和分泌的转录本丢失。沉默性促肾上腺皮质细胞瘤血管平滑肌细胞和周细胞基质细胞群体也表现出间充质特征的可塑性。
我们的研究结果为沉默性促肾上腺皮质细胞瘤中 POMC 加工缺陷和侵袭的机制提供了新的见解，并表明共同的转录重编程机制同时损害 POMC 加工并激活肿瘤侵袭。
