Translational regulation of cell invasion through extracellular matrix—an emerging role for ribosomes DOI Creative Commons
David R. Sherwood, Isabel W. Kenny-Ganzert, Siddharthan Balachandar Thendral

et al.

F1000Research, Journal Year: 2023, Volume and Issue: 12, P. 1528 - 1528

Published: Nov. 29, 2023

Many developmental and physiological processes require cells to invade migrate through extracellular matrix barriers. This specialized cellular behavior is also misregulated in many diseases, such as immune disorders cancer. Cell invasive activity driven by pro-invasive transcriptional networks that activate the expression of genes encoding numerous different proteins expand regulate cytoskeleton, endomembrane system, cell adhesion, signaling pathways, metabolic networks. While detailed mechanistic studies have uncovered crucial insights into distinct biological attributes cells, less known about how modulate mRNA translation meet robust, dynamic, unique protein production needs invasion. In this review we outline modes regulation promoting invasion focus on recent revealing elegant mechanisms ribosome biogenesis within increased requirements barriers.

Language: Английский

The actin protrusion deforms the nucleus during invasion through basement membrane DOI

Johan d’Humières,

Lianzijun Wang, David R. Sherwood

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 14, 2025

Cell invasion through basement membrane (BM) extracellular matrix barriers is important during organ development, immune cell trafficking, and cancer metastasis. Here we study an event, anchor (AC) invasion, which occurs Caenorhabditis elegans development. The actin protrusion of the invading AC mechanically displaces BM, but it not known how forces are balanced to prevent growing from pushing itself backward when confronted with a load. observe that distal end in abuts nucleus deforms it. Further show there correlation between efficiency nuclear deformation: under mutant conditions where reduced, deformation diminished. However, unaffected by interfering molecular connections microtubule cytoskeletons envelope. Together these data suggest braces against apply nucleus-cytoskeleton necessary for this occur. Actin-based protrusions cells force help break them. In motility 2D, uses cell-substrate adhesions leverage push forward obstacles what as clutch. situation different 3D adhesive substrate being effaced cell. It clear, case, why doesn't backwards instead extending forwards BM. presented here provide evidence invasive braced stiff, immobile nucleus, allowing growth proximal on

Language: Английский

Citations

0
De novo lipid synthesis and polarized prenylation drive cell invasion through basement membrane DOI Creative Commons
Kieop Park, Aastha Garde, Siddharthan Balachandar Thendral

et al.

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(10)

Published: July 15, 2024

To breach the basement membrane, cells in development and cancer use large, transient, specialized lipid-rich membrane protrusions. Using live imaging, endogenous protein tagging, cell-specific RNAi during Caenorhabditis elegans anchor cell (AC) invasion, we demonstrate that lipogenic SREBP transcription factor SBP-1 drives expression of fatty acid synthesis enzymes POD-2 FASN-1 prior to invasion. We show phospholipid-producing LPIN-1 sphingomyelin synthase SMS-1, which acids as substrates, produce lysosome stores build AC’s invasive protrusion, SMS-1 also promotes protrusion localization lipid raft partitioning ZMP-1 matrix metalloproteinase. Finally, discover HMG-CoA reductase HMGR-1, generates isoprenoids for prenylation, localizes ER enriches peroxisomes at AC front, final transmembrane prenylation enzyme, ICMT-1, endoplasmic reticulum exit sites dynamically polarize deliver prenylated GTPases formation. Together, these results reveal a collaboration between lipogenesis polarized system

Language: Английский

Citations

3
Tissue-specific RNA-seq defines genes governing male tail tip morphogenesis inC. elegans DOI Creative Commons
Karin Kiontke, Rossana Herrera, D. Adam Mason

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 12, 2024

males undergo sex-specific tail tip morphogenesis (TTM) under the control of transcription factor DMD-3. To find genes regulated by DMD-3, We performed RNA-seq laser-dissected tips. identified 564 differentially expressed (DE) in wild-type vs.

Language: Английский

Citations

2
An mTurq2-Col4a1 mouse model allows for live visualization of mammalian basement membrane development DOI Creative Commons
Rebecca A. Jones, Brandon Trejo, Parijat Sil

et al.

The Journal of Cell Biology, Journal Year: 2023, Volume and Issue: 223(2)

Published: Dec. 5, 2023

Basement membranes (BMs) are specialized sheets of extracellular matrix that underlie epithelial and endothelial tissues. BMs regulate the traffic cells molecules between compartments, participate in signaling, cell migration, organogenesis. The dynamics mammalian BMs, however, poorly understood, largely due to a lack models which core BM components endogenously labeled. Here, we describe mTurquoise2-Col4a1 mouse fluorescently tag collagen IV, main component BMs. Using an innovative planar-sagittal live imaging technique visualize developing skin, directly observe deformation during hair follicle budding basal progenitor divisions. BM's inherent pliability enables dividing remain attached deform BM, rather than lose adhesion as generally thought. FRAP, show IV is extremely stable, even periods rapid epidermal growth. These findings demonstrate utility mTurq2-Col4a1 shed new light on developmental dynamics.

Language: Английский

Citations

6
Repurposing mebendazole against triple-negative breast cancer leptomeningeal disease DOI Creative Commons
Adrian Rodrigues, Sophia B. Chernikova, Yuelong Wang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 5, 2024

Abstract Purpose Triple-negative breast cancer (TNBC) is an aggressive subtype that often metastasizes to the brain. Leptomeningeal disease (LMD), a devastating brain metastasis common in TNBC, has limited treatment options. We sought test whether anti-helminthic drug mebendazole (MBZ) may be effective against murine TNBC LMD. Methods A small-molecule screen involving cell lines identified benzimidazoles as potential therapeutic agents for further study. In vitro migration assays were used evaluate capacity and effect of MBZ. For vivo testing, LMD was introduced into BALB/c athymic nude mice through internal carotid artery injections brain-tropic MDA-MB-231-BR or MCF7-BR cells. Tumor growth spread monitored by bioluminescence imaging. MBZ given orally at 50 100 mg/kg doses. bioavailability assayed mass spectrometry. Results Bioinformatic analysis revealed higher migratory compared other subtypes. effectively slowed down line MDA-MB-231 its tropic derivative MDA-MB-231-BR. animal studies, reduced tumor extended survival model produced did not have non-migratory model. Conclusions demonstrated safe oral agent Our findings are concordant with previous efforts central nervous system pathology support drug’s utility alternative

Language: Английский

Citations

0
De novo lipid synthesis and polarized prenylation drives cell invasion through basement membrane DOI Open Access
Kieop Park, Aastha Garde, Siddharthan Balachandar Thendral

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 21, 2024

Abstract Summary Invasive cells form large, specialized protrusions to break through basement membrane (BM) matrix barriers. Park et al., reveal a crucial requirement for de novo lipid synthesis and dynamic polarizing prenylation system rapidly construct invasive that breach BMs. To (BM), in development cancer use transient, lipid-rich protrusions. Using live imaging, endogenous protein tagging, cell-specific RNAi during C. elegans anchor cell (AC) invasion, we demonstrate the lipogenic SREBP transcription factor SBP-1 drives expression of fatty acid enzymes POD-2 FASN-1 prior invasion. We show phospholipid producing LPIN-1 sphingomyelin synthase SMS-1, which acids as substrates, produce lysosome stores build AC’s protrusion, SMS-1 also promotes protrusion localization raft partitioning ZMP-1 metalloproteinase. Finally, discover endoplasmic reticulum (ER)-associated HMG-CoA reductase HMGR-1, generates isoprenoids prenylation, enriches at AC front, final ER enzyme, ICMT-1, localizes exit sites dynamically polarize deliver prenylated GTPases formation. Together, these results collaboration between lipogenesis polarized

Language: Английский

Citations

0
Repurposing mebendazole against triple-negative breast cancer CNS metastasis DOI Creative Commons
Adrian Rodrigues, Sophia B. Chernikova, Yuelong Wang

et al.

Journal of Neuro-Oncology, Journal Year: 2024, Volume and Issue: 168(1), P. 125 - 138

Published: April 2, 2024

Abstract Purpose Triple-negative breast cancer (TNBC) often metastasizes to the central nervous system (CNS) and has highest propensity among subtypes develop leptomeningeal disease (LMD). LMD is a spread of into space that speeds up progression severely aggravates prognosis. limited treatment options. We sought test whether common anti-helminthic drug mebendazole (MBZ) may be effective against murine TNBC LMD. Methods A small-molecule screen involving cell lines identified benzimidazoles as potential therapeutic agents for further study. In vitro migration assays were used evaluate capacity effect MBZ. For in vivo testing, CNS metastasis was introduced BALB/c athymic nude mice through internal carotid artery injections brain-tropic MDA-MB-231-BR or MCF7-BR cells. Tumor growth monitored by bioluminescence imaging immunohistochemistry. MBZ given orally at 50 100 mg/kg doses. bioavailability assayed mass spectrometry. Results Bioinformatic analysis revealed higher migratory compared other subtypes. effectively slowed down line MDA-MB-231 its brain tropic derivative MDA-MB-231-BR. animal studies, reduced spread, extended survival model produced did not have an non-migratory model. Conclusions demonstrated safe oral agent metastasis. Our findings are concordant with previous efforts pathology support drug’s utility slow spread.

Language: Английский

Citations

0
The Pax transcription factor EGL-38 links EGFR signaling to assembly of a cell-type specific apical extracellular matrix in theCaenorhabditis elegansvulva DOI Creative Commons
Helen Schmidt,

Chelsea B Darwin,

Meera V. Sundaram

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 7, 2024

The surface of epithelial tissues is covered by an apical extracellular matrix (aECM). aECMs different have distinct compositions to serve functions, yet how a particular cell type assembles the proper aECM not well understood. We used cell-type specific

Language: Английский

Citations

0
Tissue-specific RNA-seq defines genes governing male tail tip morphogenesis in C. elegans DOI Creative Commons
Karin Kiontke, Rossana Herrera, D. Adam Mason

et al.

Development, Journal Year: 2024, Volume and Issue: 151(18)

Published: Sept. 10, 2024

Caenorhabditis elegans males undergo sex-specific tail tip morphogenesis (TTM) under the control of DM-domain transcription factor DMD-3. To find genes regulated by DMD-3, we performed RNA-seq laser-dissected tips. We identified 564 differentially expressed (DE) in wild-type versus dmd-3(-) and hermaphrodites. The profile tips is similar to that For validation, analyzed transcriptional reporters for 49 found male-specific or male-biased expression 26 genes. Only 11 DE overlapped with a previous RNAi screen defective TTM. GO enrichment analysis finds upregulation within unfolded protein response pathway downregulation involved cuticle maintenance. Of genes, 40 are factors, indicating gene network downstream DMD-3 complex potentially modular. propose modules act together TTM co-regulated among them chondroitin synthesis hypertonic stress response.

Language: Английский

Citations

0
Lipid synthesis leads the way for invasive migration DOI
Laura M. Machesky

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(10)

Published: Sept. 10, 2024

Invasive migration requires cells to break through extracellular matrix barriers, which is an energy-expensive process. In this issue, Park et al. (https://doi.org/10.1083/jcb.202402035) highlight the importance of biosynthesis fatty acids, phospholipids, and isoprenoids in driving invasive Caenorhabditis elegans anchor cell a basement membrane barrier during development.

Language: Английский

Citations

0