Loss of lamin A/C expression in stage II and III colon cancer is associated with disease recurrence

Belt, Eric; Fijneman, Remond J.A.; Berg, Erika Gebel; Bril, Herman; Diemen, Pien M. Delis-van; Tijssen, Marianne; Essen, Hendrik F. van; Klerk, Elly S.M. de Lange–de; Beliën, Jeroen A.M.; Stockmann, H. B. A. C.; Meijer, Sybren; Meijer, Gerrit A.

doi:10.1016/j.ejca.2011.04.025

Cited by 106 publications

(95 citation statements)

References 28 publications

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“…interestingly, lamin-A/C, a protein of the nuclear envelope, was present and upregulated in the crude membrane extract from DHa-treated cells. In stage Ⅱ and Ⅲ colon cancer patients, low expression of lamin-A/C was associated with an increased disease recurrence (30). in breast cancer, it has been shown that higher lamin-A/C expression is associated with: i) early clinical stage; ⅱ) a better clinical outcomes; and ⅲ) a better overall and disease-free survival, suggesting a significant role for nuclear and chromosomal stability in this pathology (31).…”

Section: Discussionmentioning

confidence: 99%

Docosahexaenoic acid inhibits the invasion of MDA-MB-231 breast cancer cells through upregulation of cytokeratin-1

Blanckaert

Kerviel

Lepinay

et al. 2015

International Journal of Oncology

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Abstract. Docosahexaenoic acid (DHa), the main member of the omega-3 essential fatty acid family, has been shown to reduce the invasion of the triple-negative breast cancer cell line MDa-MB-231, but the mechanism involved remains unclear. In the present study, a proteomic approach was used to define changes in protein expression induced by DHa. Proteins from crude membrane preparations of MDa-MB-231 cells treated with 100 µM DHa were separated by two-dimensional electrophoresis (2-De) and differentially expressed proteins were identified using MALDI-TOF mass spectrometry. The main changes observed were the upregulation of Keratin, type Ⅱ cytoskeletal 1 (KRT1), catalase and lamin-A/C. immunocytochemistry analyses confirmed the increase in Krt1 induced by DHa. furthermore, in vitro invasion assays showed that sirna against Krt1 was able to reverse the DHa-induced inhibition of breast cancer cell invasion. in conclusion, Krt1 is involved in the anti-invasive activity of DHa in breast cancer cells.

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Section: Discussionmentioning

confidence: 99%

Docosahexaenoic acid inhibits the invasion of MDA-MB-231 breast cancer cells through upregulation of cytokeratin-1

Blanckaert

Kerviel

Lepinay

et al. 2015

International Journal of Oncology

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“…Prominin-1 (PROM1, also known as CD133) has been studied extensively as a marker for colon cancer-initiating cells and has prognostic value to predict patient survival (43,44). Lamin A/C (LMNA) is a nuclear envelope protein that has been described as a risk biomarker for CRC (45,46). TOP2A interacts with the b-catenin/TCF-4 nuclear complex of the Wnt signaling pathway (47) and can be targeted by chemotherapeutic drugs such as etoposide and doxorubicin.…”

Section: Discussionmentioning

confidence: 99%

Proximal Fluid Proteome Profiling of Mouse Colon Tumors Reveals Biomarkers for Early Diagnosis of Human Colorectal Cancer

Fijneman

Wit

Pourghiasian

et al. 2012

Clinical Cancer Research

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Purpose: Early detection of colorectal cancer (CRC) and its precursor lesions is an effective approach to reduce CRC mortality rates. This study aimed to identify novel protein biomarkers for the early diagnosis of CRC.Experimental Design: Proximal fluids are a rich source of candidate biomarkers as they contain high concentrations of tissue-derived proteins. The FabplCre;Apc 15lox/þ mouse model represents early-stage development of human sporadic CRC. Proximal fluids were collected from normal colon and colon tumors and subjected to in-depth proteome profiling by tandem mass spectrometry. Carcinoembryonic antigen (CEA) and CHI3L1 human serum protein levels were determined by ELISA.Results: Of the 2,172 proteins identified, quantitative comparison revealed 192 proteins that were significantly (P < 0.05) and abundantly (>5-fold) more excreted by tumors than by controls. Further selection for biomarkers with highest specificity and sensitivity yielded 52 candidates, including S100A9, MCM4, and four other proteins that have been proposed as candidate biomarkers for human CRC screening or surveillance, supporting the validity of our approach. For CHI3L1, we verified that protein levels were significantly increased in sera from patients with adenomas and advanced adenomas compared with control individuals, in contrast to the CRC biomarker CEA.Conclusion: These data show that proximal fluid proteome profiling with a mouse tumor model is a powerful approach to identify candidate biomarkers for early diagnosis of human cancer, exemplified by increased CHI3L1 protein levels in sera from patients with CRC precursor lesions.

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“…Other work has shown that the ability of myosin-II to deform the nucleus can be a decisive factor in limiting glioma migration into brain tissue (Beadle et al, 2008;Ivkovic et al, 2012), but cancer cells in general show no universal lamina phenotype (reviewed in Foster et al, 2010). Although low levels of A-type lamin have been correlated with increased reoccurrence of colon cancers (Belt et al, 2011), A-type lamin was also found to be upregulated in certain skin and ovarian cancers (Hudson et al, 2007;Tilli et al, 2003), and higher expression of these lamin proteins has been associated with better clinical outcomes in breast cancer (Wazir et al, 2013). Our own studies of tumor expansion in mouse flank have been suggestive of an association between moderately reduced levels of A-type lamin and increased invasiveness into the surrounding tissue, but a more complex relationship between the level of A-type lamin and clinical prognosis might be explained by the tenuous balance between the effect of the lamina on nuclear deformability compared with that on cell survival.…”

Section: Mechanotransduction To the Nucleus -Downstream Of Ecm And Laminmentioning

confidence: 99%

The nuclear lamina is mechano-responsive to ECM elasticity in mature tissue

Swift

Discher

2014

Journal of Cell Science

186

165

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How cells respond to physical cues in order to meet and withstand the physical demands of their immediate surroundings has been of great interest for many years, with current research efforts focused on mechanisms that transduce signals into gene expression. Pathways that mechano-regulate the entry of transcription factors into the cell nucleus are emerging, and our most recent studies show that the mechanical properties of the nucleus itself are actively controlled in response to the elasticity of the extracellular matrix (ECM) in both mature and developing tissue. In this Commentary, we review the mechano-responsive properties of nuclei as determined by the intermediate filament lamin proteins that line the inside of the nuclear envelope and that also impact upon transcription factor entry and broader epigenetic mechanisms. We summarize the signaling pathways that regulate lamin levels and cell-fate decisions in response to a combination of ECM mechanics and molecular cues. We will also discuss recent work that highlights the importance of nuclear mechanics in niche anchorage and cell motility during development, hematopoietic differentiation and cancer metastasis, as well as emphasizing a role for nuclear mechanics in protecting chromatin from stress-induced damage.

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Loss of lamin A/C expression in stage II and III colon cancer is associated with disease recurrence

Abstract: These data indicate that low expression of LMNA is associated with an increased disease recurrence in stage II and III colon cancer patients, and suggest that these patients in particular may benefit from adjuvant chemotherapy.

Cited by 106 publications

References 28 publications

Docosahexaenoic acid inhibits the invasion of MDA-MB-231 breast cancer cells through upregulation of cytokeratin-1

Docosahexaenoic acid inhibits the invasion of MDA-MB-231 breast cancer cells through upregulation of cytokeratin-1

Proximal Fluid Proteome Profiling of Mouse Colon Tumors Reveals Biomarkers for Early Diagnosis of Human Colorectal Cancer

The nuclear lamina is mechano-responsive to ECM elasticity in mature tissue

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