The role of Lamin A in cytoskeleton organization in colorectal cancer cells

Foster, Clare R; Robson, Joanne; Simon, William J.; Twigg, Jeremy; Cruikshank, Derek; Wilson, Robert; Hutchison, Chris

doi:10.4161/nucl.2.5.17775

Cited by 26 publications

(26 citation statements)

References 52 publications

(57 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increased LMDMs correlate with more aggressive neoplastic behavior [11]. Similarly, overexpression of lamin A/C is also seen in the context of colonic cancer [34]. In this context, lamin A/C are thought to enable cell motility, thus contributing to increased aggressiveness of the disease [35].…”

Section: Discussionmentioning

confidence: 99%

The clinicopathological significance of lamin A/C, lamin B1 and lamin B receptor mRNA expression in human breast cancer

Wazir¹,

Ahmed²,

Bridger³

et al. 2013

Cellular and Molecular Biology Letters

View full text Add to dashboard Cite

Lamin A/C (LMNA), lamin B1 (LMNB1) and lamin B receptor (LBR) have key roles in nuclear structural integrity and chromosomal stability. In this study, we have studied the relationships between the mRNA expressions of A-type lamins, LMNB1 and LBR and the clinicopathological parameters in human breast cancer. Samples of breast cancer tissues (n = 115) and associated non-cancerous tissue (ANCT; n = 30) were assessed using reverse transcription and quantitative PCR. Transcript levels were correlated with clinicopathological data. Higher levels of A-type lamins and LMNB1 mRNA expression were seen in ANCT. Higher lamin A/C expression was associated with the early clinical stage (TNM1 vs. TNM3 — 13 vs. 0.21; p = 0.0515), with better clinical outcomes (disease-free survival vs. mortality — 11 vs. 1; p = 0.0326), and with better overall (p = 0.004) and disease-free survival (p = 0.062). The expression of LMNB1 declined with worsening clinical outcome (disease-free vs. mortalities — 0.0011 vs. 0.000; p = 0.0177). LBR mRNA expression was directly associated with tumor grade (grade 1 vs. grade 3 — 0.00 vs. 0.00; p = 0.0479) and Nottingham Prognostic Index (NPI1 vs. NPI3 — 0.00 vs. 0.00; p = 0.0551). To the best of our knowledge, this is the first study to suggest such a role for A-type lamins, lamin B1 and LBR in human breast cancer, identifying an important area for further research.

show abstract

Section: Discussionmentioning

confidence: 99%

The clinicopathological significance of lamin A/C, lamin B1 and lamin B receptor mRNA expression in human breast cancer

Wazir¹,

Ahmed²,

Bridger³

et al. 2013

Cellular and Molecular Biology Letters

View full text Add to dashboard Cite

show abstract

“…Previously reported 2-DE protein profiles of cells depleted of lamin A or expressing laminopathic mutations have revealed 10-50 differentially expressed proteins with identifiable IDs by mass spectral analysis (Chen et al, 2009;Foster et al, 2011;Magagnotti et al, 2012). In our 2-DE analysis of cells expressing GFP-tagged wild-type lamin A or mutant Q294P, 27 proteins could be identified that showed differences in expression.…”

Section: High Throughput Proteomic Analysismentioning

confidence: 67%

“…The lamina is linked to the cytoskeleton via interactions with nuclear membrane proteins termed nesprins and SUN (Sad1/ UNC-84 homology) domain proteins and disruption of this linkage can cause defects in nuclear positioning and migration during development (Starr and Han, 2003). Changes in abundance of cytoskeletal proteins have been reported in lamindepleted cells and laminopathic cells (Chen et al, 2009;Foster et al, 2011;Magagnotti et al, 2012). Changes in cytoskeletal organization are likely to affect proteins involved in intracellular transport and signalling, like zymogen granule protein 16B and guanine nucleotide binding protein subunit β2 which were reduced in the mutant cells.…”

Section: Cytoskeletal Proteinsmentioning

confidence: 99%

“…In HeLa cells depleted of lamin A protein by RNA interference, hnRNP proteins like hnRNP-K and hnRNP-C1/C2 and the cytoskeletal proteins keratin and actin were also downregulated (Chen et al, 2009), whereas the protein profile of a colorectal cell line (SW480) depleted of lamin A showed decrease in nucleophosmin, HSPD1 and HSPA9, and upregulation of β-actin and vimentin (Foster et al, 2011). In a proteomic study with skin fibroblasts from patients with neuromuscular laminopathies, proteins downregulated in the patients cells which were also reduced in our lamin mutant Q294P samples included α-enolase, HSP90, hnRNP C1/C2, L-lactate dehydogenase B chain, vimentin and β-tubulin (Magagnotti et al, 2012).…”

Section: Laminsmentioning

confidence: 99%

“…Lamin mutations have been proposed to alter nuclear mechanics, impair gene regulation and cause enhanced proteosomal degradation (Parnaik et al, 2011;Butin-Israeli et al, 2012). Two-dimensional protein profiles of cells with reduced lamin levels or cells from patients with neuromuscular laminopathies have revealed alterations in heat shock proteins, hnRNPs, metabolic pathways and cytoskeletal organization (Chen et al, 2009;Foster et al, 2011;Magagnotti et al, 2012).…”

Section: K Sinha Et Almentioning

confidence: 99%

See 2 more Smart Citations

Identification of Markers for Cellular Stress and Senescence in Laminopathic Cells by Proteomic Analysis

Sinha¹,

Swamy²,

Muralikrishna³

et al. 2014

Proceedings of the Indian National Science Academy

View full text Add to dashboard Cite

Lamins are components of the structural network in the nucleus and play a key role in nuclear organization and function. Mutations in the human lamin A gene cause a spectrum of genetic diseases that include muscular dystrophies, cardiomyopathy, lipodystrophy and premature ageing syndromes. Laminopathic cells display several abnormalities in nuclear morphology and function. We have carried out a comprehensive analysis of alterations in the protein profiles of HEK293T cells expressing a mutation in lamin A (Q294P) that causes Emery-Dreifuss muscular dystrophy, in comparison with cells expressing wild-type lamin A. Initially a total of 27 differentially expressed proteins were identified by quantitative two-dimensional gel electrophoresis followed by mass spectral analysis. Importantly, a 5-fold decrease in lamin B1 levels in mutant cells was observed by quantitative two-dimensional gel electrophoresis, which was supported by immunofluorescence analysis. Changes in levels of specific heat shock proteins, hnRNPs, DNA damage response proteins, metabolic enzymes and cytoskeletal proteins were also observed. Further detailed analysis of cell lysates by one-dimensional gel electrophoresis followed by high throughput mass spectrometry revealed 650 unique proteins from wild-type cells and 1494 unique proteins from mutant cells (with two or more than two peptide hits). Alterations in a number of proteins that are involved in chromatin structure, chromosome condensation, nucleosome assembly, epigenetic modifications, centromere organization, telomere length and DNA repair were observed. These data suggest that laminopathic cells exhibit characteristics of cellular stress and senescence, and provide new insights into the cellular basis of pathologies caused by laminopathic mutations.

show abstract

Sculpting Rupture‐Free Nuclear Shapes in Fibrous Environments

et al. 2022

View full text Add to dashboard Cite

Cytoskeleton-mediated force transmission regulates nucleus morphology. How nuclei shaping occurs in fibrous in vivo environments remains poorly understood. Here suspended nanofiber networks of precisely tunable (nm-μm) diameters are used to quantify nucleus plasticity in fibrous environments mimicking the natural extracellular matrix. Contrary to the apical cap over the nucleus in cells on 2-dimensional surfaces, the cytoskeleton of cells on fibers displays a uniform actin network caging the nucleus. The role of contractility-driven caging in sculpting nuclear shapes is investigated as cells spread on aligned single fibers, doublets, and multiple fibers of varying diameters. Cell contractility increases with fiber diameter due to increased focal adhesion clustering and density of actin stress fibers, which correlates with increased mechanosensitive transcription factor Yes-associated protein (YAP) translocation to the nucleus. Unexpectedly, large-and small-diameter fiber combinations lead to teardrop-shaped nuclei due to stress fiber anisotropy across the cell. As cells spread on fibers, diameter-dependent nuclear envelope invaginations that run the nucleus's length are formed at fiber contact sites. The sharpest invaginations enriched with heterochromatin clustering and sites of DNA repair are insufficient to trigger nucleus rupture. Overall, the authors quantitate the previously unknown sculpting and adaptability of nuclei to fibrous environments with pathophysiological implications.

show abstract

The role of Lamin A in cytoskeleton organization in colorectal cancer cells

Cited by 26 publications

References 52 publications

The clinicopathological significance of lamin A/C, lamin B1 and lamin B receptor mRNA expression in human breast cancer

The clinicopathological significance of lamin A/C, lamin B1 and lamin B receptor mRNA expression in human breast cancer

Identification of Markers for Cellular Stress and Senescence in Laminopathic Cells by Proteomic Analysis

Sculpting Rupture‐Free Nuclear Shapes in Fibrous Environments

Contact Info

Product

Resources

About