Molecular Biology Research Laboratory, School of Medicine, The University of Jordan, Amman, Jordan.
Department of Thoracic Surgery, Ruhrlandklinik, University Clinic Essen, Essen, Germany.
J Physiol. 2024 Apr;602(8):1551-1564. doi: 10.1113/JP284179. Epub 2023 Mar 23.
The Ca ion is a universal second messenger involved in many vital physiological functions including cell migration and development. To fulfil these tasks the cytosolic Ca concentration is tightly controlled, and this involves an intricate functional balance between a variety of channels and pumps of the Ca signalling machinery. Among these proteins, plasma membrane Ca ATPases (PMCAs) represent the major high-affinity Ca extrusion systems in the cell membrane that are effective in maintaining free Ca concentration at exceedingly low cytosolic levels, which is essential for normal cell function. An imbalance in Ca signalling can have pathogenic consequences including cancer and metastasis. Recent studies have highlighted the role of PMCAs in cancer progression and have shown that a particular variant, PMCA4b, is downregulated in certain cancer types, causing delayed attenuation of the Ca signal. It has also been shown that loss of PMCA4b leads to increased migration and metastasis of melanoma and gastric cancer cells. In contrast, an increased PMCA4 expression has been reported in pancreatic ductal adenocarcinoma that coincided with increased cell migration and shorter patient survival, suggesting distinct roles of PMCA4b in various tumour types and/or different stages of tumour development. The recently discovered interaction of PMCAs with basigin, an extracellular matrix metalloproteinase inducer, may provide further insights into our understanding of the specific roles of PMCA4b in tumour progression and cancer metastasis.
钙离子是一种普遍的第二信使，参与许多重要的生理功能，包括细胞迁移和发育。为了完成这些任务，细胞质钙离子浓度被严格控制，这涉及到钙离子信号机制中各种通道和泵之间复杂的功能平衡。在这些蛋白质中，质膜 Ca ATP 酶（PMCA）是细胞膜上主要的高亲和力 Ca 外排系统，能够有效地将细胞质中的游离 Ca 浓度维持在极低的水平，这对于正常细胞功能是必不可少的。Ca 信号的失衡可能会产生致病后果，包括癌症和转移。最近的研究强调了 PMCA 在癌症进展中的作用，并表明特定变体 PMCA4b 在某些癌症类型中下调，导致 Ca 信号的延迟衰减。还表明，PMCA4b 的缺失会导致黑色素瘤和胃癌细胞的迁移和转移增加。相比之下，在胰腺导管腺癌中报道了 PMCA4 的表达增加，这与细胞迁移增加和患者生存时间缩短有关，这表明 PMCA4b 在不同的肿瘤类型和/或肿瘤发展的不同阶段具有不同的作用。最近发现的 PMCA 与细胞外基质金属蛋白酶诱导因子 basigin 的相互作用，可能进一步深入了解 PMCA4b 在肿瘤进展和癌症转移中的特定作用。
