Morphological changes in the size and shape of the nucleus are highly prevalent in cancer, but the underlying molecular mechanisms and the functional relevance remain poorly understood. Nuclear envelope proteins, which can modulate nuclear shape and organization, have emerged as key components in a variety of signalling pathways long implicated in tumourigenesis and metastasis. The expression of nuclear envelope proteins is altered in many cancers, and changes in levels of nuclear envelope proteins lamins A and C are associated with poor prognosis in multiple human cancers. In this review we highlight the role of the nuclear envelope in different processes important for tumour initiation and cancer progression, with a focus on lamins A and C. Lamin A/C controls many cellular processes with key roles in cancer, including cell invasion, stemness, genomic stability, signal transduction, transcriptional regulation, and resistance to mechanical stress. In addition, we discuss potential mechanisms mediating the changes in lamin levels observed in many cancers. A better understanding of cause-and-effect relationships between lamin expression and tumour progression could reveal important mechanisms for coordinated regulation of oncogenic processes, and indicate therapeutic vulnerabilities that could be exploited for improved patient outcome.

中文翻译：

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肿瘤进展中核被膜改变的原因和后果。

核的大小和形状的形态变化在癌症中非常普遍，但是对潜在的分子机制和功能相关性的了解仍然很少。可以调节核形状和组织的核被膜蛋白已作为多种信号通路中的关键成分出现，这些信号通路长期涉及肿瘤发生和转移。在许多癌症中核被膜蛋白的表达发生了改变，核被膜蛋白lamin A和C的水平变化与多种人类癌症的不良预后有关。在本文中，我们重点介绍了核包膜在不同的过程中的作用，这些过程对于肿瘤的发生和癌症的发展非常重要，重点是lamin A和C。Lamin A / C控制着许多在癌症中具有关键作用的细胞过程，包括细胞入侵，干性，基因组稳定性，信号转导，转录调控和对机械胁迫的抵抗力。此外，我们讨论了介导在许多癌症中观察到的层粘蛋白水平变化的潜在机制。对核纤层蛋白表达与肿瘤进展之间因果关系的更好理解可能揭示了协调调控致癌过程的重要机制，并指出了可用于改善患者预后的治疗脆弱性。