Saha Institute of Nuclear Physics, Kolkata; Homi Bhabha National Institute, Mumbai.
Chittaranjan National Cancer Institute, DJ Block, Area-I, New Town, Kolkata.
Biochem Soc Trans. 2020 Oct 30;48(5):2317-2333. doi: 10.1042/BST20200713.
Lamins are type V intermediate filament proteins which are ubiquitously present in all metazoan cells providing a platform for binding of chromatin and related proteins, thereby serving a wide range of nuclear functions including DNA damage repair. Altered expression of lamins in different subtypes of cancer is evident from researches worldwide. But whether cancer is a consequence of this change or this change is a consequence of cancer is a matter of future investigation. However changes in the expression levels of lamins is reported to have direct or indirect association with cancer progression or have regulatory roles in common neoplastic symptoms like higher nuclear deformability, increased genomic instability and reduced susceptibility to DNA damaging agents. It has already been proved that loss of A type lamin positively regulates cathepsin L, eventually leading to degradation of several DNA damage repair proteins, hence impairing DNA damage repair pathways and increasing genomic instability. It is established in ovarian cancer, that the extent of alteration in nuclear morphology can determine the degree of genetic changes and thus can be utilized to detect low to high form of serous carcinoma. In this review, we have focused on ovarian cancer which is largely caused by genomic alterations in the DNA damage response pathways utilizing proteins like RAD51, BRCA1, 53BP1 which are regulated by lamins. We have elucidated the current understanding of lamin expression in ovarian cancer and its implications in the regulation of DNA damage response pathways that ultimately result in telomere deformation and genomic instability.
核纤层蛋白是 V 型中间丝蛋白，广泛存在于所有后生动物细胞中，为染色质和相关蛋白的结合提供平台，从而发挥广泛的核功能，包括 DNA 损伤修复。从全球范围的研究中可以明显看出，不同亚型癌症中核纤层蛋白的表达发生了改变。但是，这种变化是癌症的结果，还是癌症是这种变化的结果，这是未来需要进一步研究的问题。然而，核纤层蛋白表达水平的变化被报道与癌症进展有直接或间接的关系，或者在常见的肿瘤症状（如核变形增加、基因组不稳定性增加和对 DNA 损伤剂的敏感性降低）中具有调节作用。已经证明 A 型核纤层蛋白的缺失可正向调节组织蛋白酶 L，最终导致几种 DNA 损伤修复蛋白的降解，从而损害 DNA 损伤修复途径并增加基因组不稳定性。在卵巢癌中已经证实，核形态改变的程度可以决定遗传变化的程度，因此可以用于检测低到高形式的浆液性癌。在这篇综述中，我们重点关注卵巢癌，它主要是由 DNA 损伤反应途径中的基因组改变引起的，利用核纤层蛋白调节的 RAD51、BRCA1 和 53BP1 等蛋白。我们阐明了核纤层蛋白在卵巢癌中的表达及其对 DNA 损伤反应途径调节的当前认识，最终导致端粒变形和基因组不稳定性。
