{"title":"Pannexin-1 regulation of ATP release promotes the invasion of pituitary adenoma.","authors":"HuaChun Yin, XiaoShuang Tang, YuYang Peng, HuiZhong Wen, Hui Yang, Song Li, Xin Zheng, Ying Xiong","doi":"10.1007/s40618-024-02445-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Pannexin-1 (PANX1) channel participates in the development and progression of many tumor types, however, its role of PANX1 in invasive pituitary adenoma (PA) remains unknown. The current study was designed to investigate the role of PANX1 in invasion of PA.</p><p><strong>Methods: </strong>We examined the expression of PANX1 in 116 surgical invasion and non-invasion PA samples (60 for bulk transcriptome and 56 for immunohistochemistry). The effects of PANX1 on PA growth were assessed in vitro and xenograft models. Meanwhile, the metabolism changes of PA cells are explored via transcriptomics and metabolomics using integration strategy.</p><p><strong>Results: </strong>PANX1 is significantly upregulated in invasive PA compared with noninvasive PA and pituitary gland, and have a potential diagnostic signature for invasive PA. Accordingly, overexpression of PANX1 could promote the proliferation and invasion of GH3 and MMQ cell lines in vitro and in vivo. Further metabolomics results confirme that overexpression of PANX1 could trigger changes in several metabolic pathways of GH3 cells. Among the dysregulated cellular metabolites, decreased intracellular ATP suggeste that PANX1 may promote the invasion of PA through impacting extracellular ATP concentration. Mechanistically, extracellular ATP might promote Ca<sup>2+</sup> influx and upregulated the expression of MMP2/9 by activating P2X7R. Additionally, PANX1-ATP-P2 X7R signaling pathway might enhance GH3 cell invasion by remodeling the actin cytoskeleton.</p><p><strong>Conclusion: </strong>Our findings point to a pivotal role of PANX1 in promoting PA invasion, which indicated a potential therapeutic target for invasive PA.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":5.4000,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Endocrinological Investigation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40618-024-02445-9","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
Purpose: Pannexin-1 (PANX1) channel participates in the development and progression of many tumor types, however, its role of PANX1 in invasive pituitary adenoma (PA) remains unknown. The current study was designed to investigate the role of PANX1 in invasion of PA.
Methods: We examined the expression of PANX1 in 116 surgical invasion and non-invasion PA samples (60 for bulk transcriptome and 56 for immunohistochemistry). The effects of PANX1 on PA growth were assessed in vitro and xenograft models. Meanwhile, the metabolism changes of PA cells are explored via transcriptomics and metabolomics using integration strategy.
Results: PANX1 is significantly upregulated in invasive PA compared with noninvasive PA and pituitary gland, and have a potential diagnostic signature for invasive PA. Accordingly, overexpression of PANX1 could promote the proliferation and invasion of GH3 and MMQ cell lines in vitro and in vivo. Further metabolomics results confirme that overexpression of PANX1 could trigger changes in several metabolic pathways of GH3 cells. Among the dysregulated cellular metabolites, decreased intracellular ATP suggeste that PANX1 may promote the invasion of PA through impacting extracellular ATP concentration. Mechanistically, extracellular ATP might promote Ca2+ influx and upregulated the expression of MMP2/9 by activating P2X7R. Additionally, PANX1-ATP-P2 X7R signaling pathway might enhance GH3 cell invasion by remodeling the actin cytoskeleton.
Conclusion: Our findings point to a pivotal role of PANX1 in promoting PA invasion, which indicated a potential therapeutic target for invasive PA.
目的：PANnexin-1（PANX1）通道参与多种肿瘤类型的发生和发展，但PANX1在侵袭性垂体腺瘤（PA）中的作用仍不清楚。本研究旨在探讨 PANX1 在侵袭性垂体腺瘤中的作用：方法：我们检测了 116 例手术侵袭性和非侵袭性 PA 样本中 PANX1 的表达（60 例为大量转录组，56 例为免疫组化）。在体外和异种移植模型中评估了PANX1对PA生长的影响。同时，利用整合策略，通过转录组学和代谢组学探讨了PA细胞的代谢变化：结果：与非侵袭性 PA 和垂体相比，PANX1 在侵袭性 PA 中明显上调，并有可能成为侵袭性 PA 的诊断标志。因此，PANX1的过表达可促进GH3和MMQ细胞株在体外和体内的增殖和侵袭。进一步的代谢组学研究结果证实，PANX1的过表达会引发GH3细胞的多种代谢途径发生变化。在失调的细胞代谢物中，细胞内 ATP 的减少表明 PANX1 可能通过影响细胞外 ATP 的浓度来促进 PA 的入侵。从机制上讲，细胞外 ATP 可能会促进 Ca2+ 流入，并通过激活 P2X7R 上调 MMP2/9 的表达。此外，PANX1-ATP-P2 X7R 信号通路可能会通过重塑肌动蛋白细胞骨架来增强 GH3 细胞的侵袭能力：我们的研究结果表明，PANX1 在促进 PA 侵袭中起着关键作用，这表明它是侵袭性 PA 的潜在治疗靶点。
期刊介绍：
The Journal of Endocrinological Investigation is a well-established, e-only endocrine journal founded 36 years ago in 1978. It is the official journal of the Italian Society of Endocrinology (SIE), established in 1964. Other Italian societies in the endocrinology and metabolism field are affiliated to the journal: Italian Society of Andrology and Sexual Medicine, Italian Society of Obesity, Italian Society of Pediatric Endocrinology and Diabetology, Clinical Endocrinologists’ Association, Thyroid Association, Endocrine Surgical Units Association, Italian Society of Pharmacology.
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