Nuclear Lamins in Cancer

Irianto, Jerome; Pfeifer, Charlotte R.; Ivanovska, Irena L.; Swift, Joe; Discher, Dennis E.

doi:10.1007/s12195-016-0437-8

Cited by 97 publications

(81 citation statements)

References 97 publications

(113 reference statements)

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“…Lamin levels, especially those of lamin A/C, determine the stiffness of the nucleus and its susceptibility to mechanical strain [24, 37, 40]. Many cancers cells have substantial alterations in lamin A/C levels [43, 44]. Mutations in the lamin genes, particularly LMNA , cause a broad spectrum of diseases called laminopathies.…”

Section: Genomic Instability In Cancermentioning

confidence: 99%

Bursting the Bubble – Nuclear Envelope Rupture as a Path to Genomic Instability?

Shah

Wolf

Lammerding

2017

Trends in Cell Biology

102

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The nuclear envelope safeguards the genetic material inside the nucleus by separating it from the cytoplasm. Until recently, it was assumed that nuclear envelope breakdown occurs only in a highly controlled fashion during mitosis when the chromatin is condensed and divided between the daughter cells. However, recent studies have demonstrated that adherent and migrating cells exhibit transient nuclear envelope rupture during interphase caused by compression from cytoskeletal or external forces. Nuclear envelope rupture results in uncontrolled exchange between the nuclear interior and cytoplasm and leads to DNA damage. In this review, we discuss the causes and consequences of nuclear envelope rupture, and how nuclear envelope rupture could contribute to genomic instability.

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Section: Genomic Instability In Cancermentioning

confidence: 99%

Bursting the Bubble – Nuclear Envelope Rupture as a Path to Genomic Instability?

Shah

Wolf

Lammerding

2017

Trends in Cell Biology

102

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“…Recent studies suggest that lamins could play important roles both upstream and downstream of this mechanosensitive process (Irianto et al, 2016). Since lamins and emerin play a central role in the mechanoregulation of gene expression, changes in lamin levels could influence how cells interpret and respond to changes in their mechanical environment.…”

Section: Lamins and The Mechanical Tumour Microenvironmentmentioning

confidence: 99%

Causes and consequences of nuclear envelope alterations in tumour progression

Bell

Lammerding

2016

European Journal of Cell Biology

110

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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.

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“…However, the increase of rupture frequency with substrate stiffness has been observed only in cells with defects in lamin-A, which is one of the three intermediate filament proteins that confer strength and stability to the nucleus. Yet, cancer types vary widely in their lamin-A expression levels: it is downregulated in leukemia as well as in breast and lung cancers, whereas it is upregulated in colorectal and skin cancers (for review: [46]). Lamin-A is highly mutated in multiple laminopathies, but cancer risk is not reported to be elevated.…”

Section: Mechanical Causes Of Mutation In the Correlation Of Genomic mentioning

confidence: 99%

Genome variation across cancers scales with tissue stiffness – An invasion-mutation mechanism and implications for immune cell infiltration

Pfeifer

Alvey

Irianto

et al. 2017

Current Opinion in Systems Biology

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Many different types of soft and solid tumors have now been sequenced, and meta-analyses suggest that genomic variation across tumors scales with the stiffness of the tumors’ tissues of origin. The opinion expressed here is based on a review of current genomics data, and it considers multiple ‘mechanogenomics’ mechanisms to potentially explain this scaling of mutation rate with tissue stiffness. Since stiff solid tissues have higher density of fibrous collagen matrix, which should decrease tissue porosity, cancer cell proliferation could be affected and so could invasion into stiff tissues as the nucleus is squeezed sufficiently to enhance DNA damage. Diversification of a cancer genome after constricted migration is now clear. Understanding genome changes that give rise to neo-antigens is important to selection as well as to the development of immunotherapies, and we discuss engineered monocytes/macrophages as particularly relevant to understanding infiltration into solid tumors.

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Nuclear Lamins in Cancer

Cited by 97 publications

References 97 publications

Bursting the Bubble – Nuclear Envelope Rupture as a Path to Genomic Instability?

Bursting the Bubble – Nuclear Envelope Rupture as a Path to Genomic Instability?

Causes and consequences of nuclear envelope alterations in tumour progression

Genome variation across cancers scales with tissue stiffness – An invasion-mutation mechanism and implications for immune cell infiltration

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