A novel role of lamins from genetic disease to cancer biomarkers

Sakthivel, Kunnathur Murugesan; Sehgal, Poonam

doi:10.4081/oncol.2016.309

Cited by 54 publications

(66 citation statements)

References 62 publications

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“…Although nothing is known about LMNA phosphorylation and cancer aggressive feature, since lamins recently emerged as potential cell mechanosensors with a potential cellular role of phospho-LMNA during stress (Torvaldson, Kochin, & Eriksson, 2015), it is tempting to speculate that the increased phosphorylated LMNA could be associated with cytoskeleton modification and the other protein alterations identified in CPr-A549 cells, thereby facilitating EMT and increased invasion ability. We also found the upregulation of LMNB1, another important member of the lamin proteins family, which is generally overexpressed in most of the lung cancers (Sakthivel & Sehgal, 2016), even if its specific role in cancer development and progression is unclear.…”

Section: Discussionmentioning

confidence: 68%

“…Among the identified differentially expressed proteins, we found VIM more than three-fold overexpressed in CPr-A549 compared of LMNA expression was associated with increased malignancy of lung cancer and was proposed as a biomarker of lung cancer for early detection (Sakthivel & Sehgal, 2016). LMNA is subjected to numerous post translational modifications, most prominently phosphorylation, and in CPr-A549 cells we also found upregulation of phospho-LMNA.…”

Section: Discussionmentioning

confidence: 69%

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Novel pathways involved in cisplatin resistance identified by a proteomics approach in non‐small‐cell lung cancer cells

Milone

Lombardi

Roca

et al. 2018

Journal Cellular Physiology

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Although platinum‐based chemotherapy remains the standard‐of‐care for most patients with advanced non‐small‐cell lung cancer (NSCLC), acquired resistance occurs frequently predicting poor prognosis. To examine the mechanisms underlying platinum resistance, we have generated and characterized by proteomic approach the resistant A549 CDDP‐resistant (CPr‐A549) and their parental A549 cells, identifying 15 proteins differentially expressed (13 upregulated and 2 downregulated in CPr‐A549). In details, we highlighted a coherent network of proteins clustering together and involved in altered protein folding and endoplasmic reticulum stress, correlated with epithelial to mesenchymal transition process and cancer stem cell markers, where vimentin played a hierarchical role, ultimately resulting in increased aggressive features. By using publicly available databases we showed that the modulated proteins could contribute to NSCLC carcinogenesis and correlate with NSCLC patients prognosis and survival probability, suggesting that they can be used as novel potential prognostic/predictive biomarkers or therapeutic targets to overcome platinum‐resistance.

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Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 69%

Novel pathways involved in cisplatin resistance identified by a proteomics approach in non‐small‐cell lung cancer cells

Milone

Lombardi

Roca

et al. 2018

Journal Cellular Physiology

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“…Mutations in the LMNA gene and/or alterations in its expression levels have been linked to a variety of distinct degenerative diseases, collectively known as the laminopathies, and to cancer (Burke & Stewart, ; Sakthivel & Sehgal, ).…”

Section: Introductionmentioning

confidence: 99%

Smurf2 regulates stability and the autophagic–lysosomal turnover of lamin A and its disease‐associated form progerin

et al. 2018

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SummaryA‐lamins, encoded by the LMNA gene, are major structural components of the nuclear lamina coordinating essential cellular processes. Mutations in the LMNA gene and/or alterations in its expression levels have been linked to a distinct subset of human disorders, collectively known as laminopathies, and to cancer. Mechanisms regulating A‐lamins are mostly obscure. Here, we identified E3 ubiquitin ligase Smurf2 as a physiological regulator of lamin A and its disease‐associated mutant form progerin (LAΔ50), whose expression underlies the development of Hutchinson‐Gilford progeria syndrome (HGPS), a devastating premature aging syndrome. We show that Smurf2 directly binds, ubiquitinates, and negatively regulates the expression of lamin A and progerin in Smurf2 dose‐ and E3 ligase‐dependent manners. Overexpression of catalytically active Smurf2 promotes the autophagic–lysosomal breakdown of lamin A and progerin, whereas Smurf2 depletion increases lamin A levels. Remarkably, acute overexpression of Smurf2 in progeria fibroblasts was able to significantly reduce the nuclear deformability. Furthermore, we demonstrate that the reciprocal relationship between Smurf2 and A‐lamins is preserved in different types of mouse and human normal and cancer tissues. These findings establish Smurf2 as an essential regulator of lamin A and progerin and lay a foundation for evaluating the efficiency of progerin clearance by Smurf2 in HGPS, and targeting of the Smurf2–lamin A axis in age‐related diseases such as cancer.

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“…Much more needs to be learned about the role that lamin A/C and other structural proteins play in cancer cells . A recent review by Sakthivel and Sehgal discusses potential roles of lamin A/C as a tumor biomarker, where increased expression is associated with aggressive colon cancer and higher Gleason scores in prostate cancer. Overexpression of lamin A/C is also found in germ cell cancer, whereas reduced expression has been reported in neuroblastoma, small‐cell lung cancer and breast cancer.…”

Section: The 3d Nucleus In Cancer Cells: Where We Are Today and Wherementioning

confidence: 99%

The three‐dimensional cancer nucleus

Mai

2019

Genes Chromosomes & Cancer

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Research into the three‐dimensional (3D) organization of the cancer cell genome started over 100 years ago. We follow an exciting avenue of research in this field, from Hansemann's early observations of aberrant mitoses and nuclei in cancer cells in the late 19th century to Boveri's theory of the cancer cell in the early 20th century, to current views of nuclear organization and its changes in cancer. Molecular and imaging methods go hand in hand with providing us with a better understanding of the spatial nature of the cancer cell genome. This has led to the concept that the structural order of the nucleus can be used as cancer cell biomarker.

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A novel role of lamins from genetic disease to cancer biomarkers

Cited by 54 publications

References 62 publications

Novel pathways involved in cisplatin resistance identified by a proteomics approach in non‐small‐cell lung cancer cells

Novel pathways involved in cisplatin resistance identified by a proteomics approach in non‐small‐cell lung cancer cells

Smurf2 regulates stability and the autophagic–lysosomal turnover of lamin A and its disease‐associated form progerin

The three‐dimensional cancer nucleus

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