Department of Human Neuroscience, Sapienza University of Rome, Via Caserta 6, 00161 Roma, Italy.
Department of Oral and Maxillofacial Sciences, Sapienza University of Rome, Via Caserta 6, 00161 Roma, Italy.
Int J Mol Sci. 2023 Jan 11;24(2):1405. doi: 10.3390/ijms24021405.
The carcinogenesis of glial tumors appears complex because of the many genetic and epigenetic phenomena involved. Among these, cellular prion protein (PrPC) is considered a key factor in cell-death resistance and important aspect implicated in tumorigenesis. Autophagy also plays an important role in cell death in various pathological conditions. These two cellular phenomena are related and share the same activation by specific alterations in the cellular microenvironment. Furthermore, there is an interdependence between autophagy and prion activity in glioma tumorigenesis. Glioma is one of the most aggressive known cancers, and the fact that such poorly studied processes as autophagy and PrPC activity are so strongly involved in its carcinogenesis suggests that by better understanding their interaction, more can be understood about its origin and treatment. Few studies in the literature relate these two cellular phenomena, much less try to explain their combined activity and role in glioma carcinogenesis. In this study, we explored the recent findings on the molecular mechanism and regulation pathways of autophagy, examining the role of PrPC in autophagy processes and how they may play a central role in glioma tumorigenesis. Among the many molecular interactions that PrP physiologically performs, it appears that processes shared with autophagy activity are those most implicated in glial tumor carcinogeneses such as activity on MAP kinases, PI3K, and mTOR. This work can be supportive and valuable as a basis for further future studies on this topic.
神经胶质瘤的发生机制较为复杂,涉及许多遗传和表观遗传现象。在这些现象中,细胞朊蛋白(PrPC)被认为是抵抗细胞死亡的关键因素,也是肿瘤发生的重要方面。自噬在各种病理条件下的细胞死亡中也起着重要作用。这两种细胞现象是相关的,并且通过细胞微环境的特定改变具有相同的激活方式。此外,自噬和朊病毒活性在神经胶质瘤的发生中存在相互依存关系。神经胶质瘤是已知的最具侵袭性的癌症之一,事实表明,自噬和 PrPC 活性等研究甚少的过程在其致癌作用中如此强烈地参与,这表明通过更好地了解它们的相互作用,可以更多地了解其起源和治疗方法。文献中很少有研究将这两种细胞现象联系起来,更不用说试图解释它们在神经胶质瘤发生中的联合活性和作用了。在这项研究中,我们探讨了自噬的分子机制和调节途径的最新发现,研究了 PrPC 在自噬过程中的作用以及它们如何在神经胶质瘤的发生中发挥核心作用。在 PrP 发挥生理作用的许多分子相互作用中,与自噬活性共享的过程似乎是与神经胶质瘤致癌作用最相关的过程,例如对 MAP 激酶、PI3K 和 mTOR 的作用。这项工作可以作为进一步研究该主题的基础,具有支持和有价值的意义。