scholarly journals Increased Lamin B1 Levels Promote Cell Migration by Altering Perinuclear Actin Organization

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2161
Author(s):  
Andrea Fracchia ◽  
Tal Asraf ◽  
Mali Salmon-Divon ◽  
Gabi Gerlitz
Keyword(s):  
Cell Migration ◽  
Actin Filaments ◽  
Migration Rate ◽  
Tumor Formation ◽  
Cellular Migration ◽  
Lamin A ◽  
Linc Complex ◽  
Actin Organization ◽  
Lamin B1 ◽  
Promote Cell Migration

Cell migration requires reposition and reshaping of the cell nucleus. The nuclear lamina is highly important for migration of both primary and cancer cells. B-type lamins are important for proper migration of epicardial cells and neurons and increased lamin B to lamin A ratio accelerates cancer cell migration through confined spaces. Moreover, a positive association between lamin B1 levels and tumor formation and progression is found in various cancer types. Still, the molecular mechanism by which B-type lamins promote cell migration is not fully understood. To better understand this mechanism, we tested the effects of lamin B1 on perinuclear actin organization. Here we show that induction of melanoma cell migration leads to the formation of a cytosolic Linker of Nucleoskeleton and Cytoskeleton (LINC) complex-independent perinuclear actin rim, which has not been detected in migrating cells, yet. Significantly, increasing the levels of lamin B1 but not the levels of lamin A prevented perinuclear actin rim formation while accelerated the cellular migration rate. To interfere with the perinuclear actin rim, we generated a chimeric protein that is localized to the outer nuclear membrane and cleaves perinuclear actin filaments in a specific manner without disrupting other cytosolic actin filaments. Using this tool, we found that disruption of the perinuclear actin rim accelerated the cellular migration rate in a similar manner to lamin B1 over-expression. Taken together, our results suggest that increased lamin B1 levels can accelerate cell migration by inhibiting the association of the nuclear envelope with actin filaments that may reduce nuclear movement and deformability.

scholarly journals Lamin B1 loss promotes lung cancer development and metastasis by epigenetic derepression of RET

2019 ◽  
Vol 216 (6) ◽  
pp. 1377-1395 ◽  
Author(s):  
Yanhan Jia ◽  
Joaquim Si-Long Vong ◽  
Alina Asafova ◽  
Boyan K. Garvalov ◽  
Luca Caputo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Nuclear Structure ◽  
Epithelial Mesenchymal Transition ◽  
Lung Tumor ◽  
Cancer Diagnostics ◽  
Tumor Formation ◽  
Lung Epithelial Cells ◽  
Mesenchymal Transition ◽  
Lamin B1

Although abnormal nuclear structure is an important criterion for cancer diagnostics, remarkably little is known about its relationship to tumor development. Here we report that loss of lamin B1, a determinant of nuclear architecture, plays a key role in lung cancer. We found that lamin B1 levels were reduced in lung cancer patients. Lamin B1 silencing in lung epithelial cells promoted epithelial–mesenchymal transition, cell migration, tumor growth, and metastasis. Mechanistically, we show that lamin B1 recruits the polycomb repressive complex 2 (PRC2) to alter the H3K27me3 landscape and repress genes involved in cell migration and signaling. In particular, epigenetic derepression of the RET proto-oncogene by loss of PRC2 recruitment, and activation of the RET/p38 signaling axis, play a crucial role in mediating the malignant phenotype upon lamin B1 disruption. Importantly, loss of a single lamin B1 allele induced spontaneous lung tumor formation and RET activation. Thus, lamin B1 acts as a tumor suppressor in lung cancer, linking aberrant nuclear structure and epigenetic patterning with malignancy.

scholarly journals Fascin in Cell Migration: More Than an Actin Bundling Protein

Biology ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 403
Author(s):  
Maureen C. Lamb ◽  
Tina L. Tootle
Keyword(s):  
Cell Migration ◽  
Protein Interactions ◽  
Cancer Metastasis ◽  
Control Cell ◽  
Actin Binding ◽  
Linc Complex ◽  
Protein Protein Interactions ◽  
Post Translational Modifications ◽  
Promote Cell Migration ◽  
The Many

Fascin, an actin-binding protein, regulates many developmental migrations and contributes to cancer metastasis. Specifically, Fascin promotes cell motility, invasion, and adhesion by forming filopodia and invadopodia through its canonical actin bundling function. In addition to bundling actin, Fascin has non-canonical roles in the cell that are thought to promote cell migration. These non-canonical functions include regulating the activity of other actin-binding proteins, binding to and regulating microtubules, mediating mechanotransduction to the nucleus via interaction with the Linker of the Nucleoskeleton and Cytoskeleton (LINC) Complex, and localizing to the nucleus to regulate nuclear actin, the nucleolus, and chromatin modifications. The many functions of Fascin must be coordinately regulated to control cell migration. While much remains to be learned about such mechanisms, Fascin is regulated by post-translational modifications, prostaglandin signaling, protein–protein interactions, and transcriptional means. Here, we review the structure of Fascin, the various functions of Fascin and how they contribute to cell migration, the mechanisms regulating Fascin, and how Fascin contributes to diseases, specifically cancer metastasis.

scholarly journals FAM83G/PAWS1 controls cytoskeletal dynamics and cell migration through association with the SH3 adaptor CD2AP

2017 ◽  
Author(s):  
Timothy D. Cummins ◽  
Kevin Z. L. Wu ◽  
Polyxeni Bozatzi ◽  
Kevin S. Dingwell ◽  
Thomas Macartney ◽  
...  
Keyword(s):  
Cell Migration ◽  
Live Cell Imaging ◽  
Focal Adhesions ◽  
Cellular Migration ◽  
Actin Organization ◽  
Actin Stress Fibre ◽  
Fibre Network ◽  
Cytoskeletal Dynamics ◽  
Summary Statement ◽  
Bmp Signalling

AbstractOur previous studies of PAWS1 (Protein Associated With SMAD1) have suggested that this molecule has roles beyond BMP signalling. To investigate these roles, we have used CRISPR/Cas9 to generate PAWS1 knockout cells. Here, we show that PAWS1 plays a role in the regulation of the cytoskeletal machinery, including actin and focal adhesion dynamics, and cell migration. Confocal microscopy and live cell imaging of actin in U2OS cells indicate that PAWS1 is also involved in cytoskeletal dynamics and organization. Loss of PAWS1 causes severe defects in F-actin organization and distribution as well as in lamellipodial organization, resulting in impaired cell migration. PAWS1 interacts in a dynamic fashion with the actin/cytoskeletal regulator CD2AP at lamellae, suggesting that its association with CD2AP controls actin organization and cellular migration.Summary statementPAWS1/FAM83G controls cell migration by influencing the organisation of F-actin and focal adhesions and the distribution of the actin stress fibre network through its association with CD2AP.

scholarly journals LINC complex independent perinuclear actin organization and cell migration

BIOCELL ◽  
2022 ◽  
Vol 46 (4) ◽  
pp. 931-935
Author(s):  
ANDREA FRACCHIA ◽  
GABI GERLITZ
Keyword(s):  
Cell Migration ◽  
Linc Complex ◽  
Actin Organization

scholarly journals Role of the V1G1 subunit of V-ATPase in breast cancer cell migration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria De Luca ◽  
Roberta Romano ◽  
Cecilia Bucci
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cell Motility ◽  
Cancer Progression ◽  
Tumor Formation ◽  
Downstream Signaling ◽  
Late Endosomes ◽  
Intracellular Compartments

AbstractV-ATPase is a large multi-subunit complex that regulates acidity of intracellular compartments and of extracellular environment. V-ATPase consists of several subunits that drive specific regulatory mechanisms. The V1G1 subunit, a component of the peripheral stalk of the pump, controls localization and activation of the pump on late endosomes and lysosomes by interacting with RILP and RAB7. Deregulation of some subunits of the pump has been related to tumor invasion and metastasis formation in breast cancer. We observed a decrease of V1G1 and RAB7 in highly invasive breast cancer cells, suggesting a key role of these proteins in controlling cancer progression. Moreover, in MDA-MB-231 cells, modulation of V1G1 affected cell migration and matrix metalloproteinase activation in vitro, processes important for tumor formation and dissemination. In these cells, characterized by high expression of EGFR, we demonstrated that V1G1 modulates EGFR stability and the EGFR downstream signaling pathways that control several factors required for cell motility, among which RAC1 and cofilin. In addition, we showed a key role of V1G1 in the biogenesis of endosomes and lysosomes. Altogether, our data describe a new molecular mechanism, controlled by V1G1, required for cell motility and that promotes breast cancer tumorigenesis.

scholarly journals Rudhira/BCAS3 couples microtubules and intermediate filaments to promote cell migration for angiogenic remodeling

2019 ◽  
Vol 30 (12) ◽  
pp. 1437-1450 ◽  
Author(s):  
Divyesh Joshi ◽  
Maneesha S. Inamdar
Keyword(s):  
Cell Migration ◽  
Intermediate Filaments ◽  
Cross Talk ◽  
Control Cell ◽  
The Novel ◽  
Mouse Development ◽  
Cytoskeleton Organization ◽  
Sprouting Angiogenesis ◽  
Promote Cell Migration ◽  
Necessary And Sufficient

Blood vessel formation requires endothelial cell (EC) migration that depends on dynamic remodeling of the cytoskeleton. Rudhira/Breast Carcinoma Amplified Sequence 3 (BCAS3) is a cytoskeletal protein essential for EC migration and sprouting angiogenesis during mouse development and is implicated in metastatic disease. Here, we report that Rudhira mediates cytoskeleton organization and dynamics during EC migration. Rudhira binds to both microtubules (MTs) and vimentin intermediate filaments (IFs) and stabilizes MTs. Rudhira depletion impairs cytoskeletal cross-talk, MT stability, and hence focal adhesion disassembly. The BCAS3 domain of Rudhira is necessary and sufficient for MT-IF cross-linking and cell migration. Pharmacologically restoring MT stability rescues gross cytoskeleton organization and angiogenic sprouting in Rudhira-depleted cells. Our study identifies the novel and essential role of Rudhira in cytoskeletal cross-talk and assigns function to the conserved BCAS3 domain. Targeting Rudhira could allow tissue-restricted cytoskeleton modulation to control cell migration and angiogenesis in development and disease.

scholarly journals The apoptotic members CD95, BclxL, and Bcl-2 cooperate to promote cell migration by inducing Ca2+ flux from the endoplasmic reticulum to mitochondria

2016 ◽  
Vol 23 (10) ◽  
pp. 1702-1716 ◽  
Author(s):  
A Fouqué ◽  
E Lepvrier ◽  
L Debure ◽  
Y Gouriou ◽  
M Malleter ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Migration ◽  
Promote Cell Migration
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