Physical Forces and Transient Nuclear Envelope Rupture during Metastasis: The Key for Success?

Gauthier, Benoit R.; Lorenzo, Petra I.; Comaills, Valentine

doi:10.3390/cancers14010083

Cited by 7 publications

(6 citation statements)

References 107 publications

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“…The deformability of the cell, as well as the nucleus, is a necessary feature for the progression of cancer metastasis. , During cancer metastasis, cancer cells pass through the basement membrane, the endothelial wall, and narrow capillaries to reach new organs. In this process, the cell body is compressed and the traction exerted by the cytoskeleton deforms the nucleus . These publications − together with others imply some relevance between nuclear deformation and EMT.…”

Section: Introductionmentioning

confidence: 77%

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Epithelial-Mesenchymal Transition of Cancer Cells on Micropillar Arrays

Liu,

Wang,

Ding

2024

ACS Appl. Bio Mater.

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Epithelial-mesenchymal transition (EMT) is critical for tumor invasion and many other cell-relevant processes. While much progress has been made about EMT, no report concerns the EMT of cells on topological biomaterial interfaces with significant nuclear deformation. Herein, we prepared a poly(lactideco-glycolide) micropillar array with an appropriate dimension to enable significant deformation of cell nuclei and examined EMT of a human lung cancer epithelial cell (A549). We show that A549 cells undergo serious nuclear deformation on the micropillar array. The cells express more E-cadherin and less vimentin on the micropillar array than on the smooth surface. After transforming growth factor-β1 (TGF-β1) treatment, the expression of E-cadherin as an indicator of the epithelial phenotype is decreased and the expression of vimentin as an indicator of the mesenchymal phenotype is increased for the cells both on smooth surfaces and on micropillar arrays, indicating that EMT occurs even when the cell nuclei are deformed and the culture on the micropillar array more enhances the expression of vimentin. Expression of myosin phosphatase targeting subunit 1 is reduced in the cells on the micropillar array, possibly affecting the turnover of myosin light chain phosphorylation and actin assembly; this makes cells on the micropillar array prefer the epithelial-like phenotype and more sensitive to TGF-β1. Overall, the micropillar array exhibits a promoting effect on the EMT.

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Section: Introductionmentioning

confidence: 77%

“…In this process, the cell body is compressed and the traction exerted by the cytoskeleton deforms the nucleus. 11 These publications 12−14 together with others imply some relevance between nuclear deformation and EMT. Nevertheless, there is, so far, no report focused on the exploration of the relation between EMT and nuclear deformation.…”

Section: Introductionmentioning

confidence: 92%

Epithelial-Mesenchymal Transition of Cancer Cells on Micropillar Arrays

Liu,

Wang,

Ding

2024

ACS Appl. Bio Mater.

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“…This implies the generation of additional tension forces affecting the NE during movement, leading to NER that can last up to two minutes [67]. Cells during migration can also experience NER of their nuclei [69][70][71][72]. Interestingly, immune attack can fail and can contribute to mutagenesis.…”

Section: Transient Nuclear Envelope Rupture (Ner)mentioning

confidence: 99%

Chromosomal Instability in Genome Evolution: From Cancer to Macroevolution

Comaills¹,

Castellano‐Pozo²

2023

Preprint

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The integrity of the genome is crucial for the survival of all living organisms. However, genomes need to adapt to survive certain pressures and for this propose use several mechanisms to diversify. Chromosomal instability (CIN) is one of the main mechanism leading to the creation of genomic heterogeneity by altering the number of chromosomes as well as changing their structures. In this review we will discuss the different chromosomal patterns and changes observed in speciation, in evolutional biology as well as during tumor progression. By nature, human genome shows induction of diversity during gametogenesis but as well during tumorigenesis that can conclude in drastic changes such as whole genome doubling to more discrete changes as indels as well as the recent discovered complex chromosomal rearrangement chromothripsis. More importantly, changes observed during speciation are strikingly similar to the genomic evolution observed during tumor progression and resistance to therapy. The different origins of CIN will be treated as the importance of double strand breaks (DSB) or the consequences of micronuclei. We will also explain the mechanisms behind the controlled DSBs and recombination of homologous chromosomes observed during meiosis, to explain how errors lead to similar pattern observed during tumorigenesis. Then, we will also list several diseases associated to CIN resulting in fertility issue, miscarriage, genetic rare diseases and cancer. Understanding better chromosomal instability as a whole is primordial for the understanding of mechanisms leading to tumor progression.

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“…After reaching secondary distant metastatic sites, CTCs extravasate from the blood circulation through enhanced endothelial intercellular gaps via endothelial morphologic changes [63] . Owing to their deformation capability facilitating the movement of CTCs through capillary beds, [64] capillary-rich organs, such as the liver, lungs, brain, and bones, are frequent sites of cancer metastases [19] . The proliferation and growth of CTCs in secondary sites can be further fueled by inflammatory factors and growth factors in the TME [65] .…”

Section: Nanomedicine-based Strategy For Remodeling the Microenvironm...mentioning

confidence: 99%

Tumor immune microenvironment-modulated nanostrategy for the treatment of lung cancer metastasis

Zhu

Gao

et al. 2023

Chinese Medical Journal

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As one of the most malignant tumors worldwide, lung cancer, fueled by metastasis, has shown rising mortality rates. However, effective clinical strategies aimed at preventing metastasis are lacking owing to its dynamic multi-step, complicated, and progressive nature. Immunotherapy has shown promise in treating cancer metastasis by reversing the immunosuppressive network of the tumor microenvironment. However, drug resistance inevitably develops due to inadequate delivery of immunostimulants and an uncontrolled immune response. Consequently, adverse effects occur, such as autoimmunity, from the non-specific immune activation and non-specific inflammation in off-target organs. Nanocarriers that improve drug solubility, permeability, stability, bioavailability, as well as sustained, controlled, and targeted delivery can effectively overcome drug resistance and enhance the therapeutic effect while reducing adverse effects. In particular, nanomedicine-based immunotherapy can be utilized to target tumor metastasis, presenting a promising therapeutic strategy for lung cancer. Nanotechnology strategies that boost the immunotherapy effect are classified based on the metastatic cascade related to the tumor immune microenvironment; the breaking away of primary tumors, circulating tumor cell dissemination, and premetastatic niche formation cause distant secondary site colonization. In this review, we focus on the opportunities and challenges of integrating immunotherapy with nanoparticle formulation to establish nanotechnology-based immunotherapy by modulating the tumor microenvironment for preclinical and clinical applications in the management of patients with metastatic lung cancer. We also discuss prospects for the emerging field and the clinical translation potential of these techniques.

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Physical Forces and Transient Nuclear Envelope Rupture during Metastasis: The Key for Success?

Cited by 7 publications

References 107 publications

Epithelial-Mesenchymal Transition of Cancer Cells on Micropillar Arrays

Epithelial-Mesenchymal Transition of Cancer Cells on Micropillar Arrays

Chromosomal Instability in Genome Evolution: From Cancer to Macroevolution

Tumor immune microenvironment-modulated nanostrategy for the treatment of lung cancer metastasis

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