文章：

质子如何为侵袭性癌症铺平道路

How protons pave the way to aggressive cancers

原文发布日期：2023-10-26

DOI: 10.1038/s41568-023-00628-9

类型: Review Article

开放获取: 否

英文摘要：

Cancers undergo sequential changes to proton (H+) concentration and sensing that are consequences of the disease and facilitate its further progression. The impact of protonation state on protein activity can arise from alterations to amino acids or their titration. Indeed, many cancer-initiating mutations influence pH balance, regulation or sensing in a manner that enables growth and invasion outside normal constraints as part of oncogenic transformation. These cancer-supporting effects become more prominent when tumours develop an acidic microenvironment owing to metabolic reprogramming and disordered perfusion. The ensuing intracellular and extracellular pH disturbances affect multiple aspects of tumour biology, ranging from proliferation to immune surveillance, and can even facilitate further mutagenesis. As a selection pressure, extracellular acidosis accelerates disease progression by favouring acid-resistant cancer cells, which are typically associated with aggressive phenotypes. Although acid–base disturbances in tumours often occur alongside hypoxia and lactate accumulation, there is now ample evidence for a distinct role of H+-operated responses in key events underpinning cancer. The breadth of these actions presents therapeutic opportunities to change the trajectory of disease.

摘要翻译： 

癌症经历质子（H+）浓度和感知的序列性变化，这些变化既是疾病的结果，又促进其进一步进展。质子化状态对蛋白质活性的影响可能源于氨基酸的改变或其滴定作用。事实上，许多癌症起始突变会以破坏pH平衡、调控或感知的方式，使细胞能够在正常限制之外生长和侵袭，成为致癌转化的一部分。当肿瘤因代谢重编程和灌注紊乱形成酸性微环境时，这些促癌效应变得尤为显著。随之而来的细胞内和细胞外pH紊乱影响肿瘤生物学的多个方面，从增殖到免疫监视，甚至可能促进进一步突变。作为选择压力，细胞外酸中毒通过偏爱耐酸癌细胞（通常与侵袭性表型相关）加速疾病进展。虽然肿瘤中的酸碱紊乱常与缺氧和乳酸积累并存，现有充分证据表明H+调控的反应在癌症关键事件中具有独特作用。这些作用的广泛性为改变疾病轨迹提供了治疗机遇。

原文链接：

How protons pave the way to aggressive cancers