Dubik Niina, Mai Sabine
Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB R3E0V9, Canada.
Cancers (Basel). 2020 Dec 9;12(12):3688. doi: 10.3390/cancers12123688.
This review is focused on lamin A/C, a nuclear protein with multiple functions in normal and diseased cells. Its functions, as known to date, are summarized. This summary includes its role in maintaining a cell's structural stability, cell motility, mechanosensing, chromosome organization, gene regulation, cell differentiation, DNA damage repair, and telomere protection. As lamin A/C has a variety of critical roles within the cell, mutations of the lamin A/C gene and incorrect processing of the protein results in a wide variety of diseases, ranging from striated muscle disorders to accelerated aging diseases. These diseases, collectively termed laminopathies, are also touched upon. Finally, we review the existing evidence of lamin A/C's deregulation in cancer. Lamin A/C deregulation leads to various traits, including genomic instability and increased tolerance to mechanical insult, which can lead to more aggressive cancer and poorer prognosis. As lamin A/C's expression in specific cancers varies widely, currently known lamin A/C expression in various cancers is reviewed. Additionally, Lamin A/C's potential as a biomarker in various cancers and as an aid in more accurately diagnosing intermediate Gleason score prostate cancers is also discussed.
本综述聚焦于核纤层蛋白A/C,一种在正常细胞和病变细胞中具有多种功能的核蛋白。总结了其目前已知的功能,包括在维持细胞结构稳定性、细胞运动、机械传感、染色体组织、基因调控、细胞分化、DNA损伤修复和端粒保护中的作用。由于核纤层蛋白A/C在细胞内具有多种关键作用,核纤层蛋白A/C基因的突变和蛋白质的错误加工会导致多种疾病,从横纹肌疾病到加速衰老疾病不等。这些疾病统称为核纤层蛋白病,也会涉及到。最后,我们综述了核纤层蛋白A/C在癌症中失调的现有证据。核纤层蛋白A/C失调会导致多种特征,包括基因组不稳定和对机械损伤的耐受性增加,这会导致更具侵袭性的癌症和更差的预后。由于核纤层蛋白A/C在特定癌症中的表达差异很大,因此综述了目前已知的其在各种癌症中的表达情况。此外,还讨论了核纤层蛋白A/C作为各种癌症生物标志物的潜力以及在更准确诊断中危格里森评分前列腺癌方面的辅助作用。