title: Causes and consequences of nuclear envelope alterations in tumour progression.
abstract: 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.
authors.affiliation: Meinig School of Biomedical Engineering & Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, United States.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Bell
authors.affiliation: Meinig School of Biomedical Engineering & Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, United States. Electronic address: jan.lammerding@cornell.edu.
authors.forename: Jan
authors.initials: J
authors.lastname: Lammerding
mesh_terms: D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D034904:Lamin Type A / Q000096:biosynthesis* / Q000235:genetics; D034882:Lamins / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009685:Nuclear Envelope / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction
chemical_list: D034904:Lamin Type A; D034882:Lamins; D009363:Neoplasm Proteins; C000605834:lamin C protein, human
keywords: Cancer; Cell mechanics; Cell migration; Gene regulation; Lamins; Signal transduction