Cell invasion through basement membrane

Morrissey, Meghan A.; Hagedorn, Elliott J.; Sherwood, David R.

doi:10.4161/worm.26169

Cited by 25 publications

(24 citation statements)

References 50 publications

(67 reference statements)

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“…Following BM penetration, invadopodia formation ceases, and a large, longer-lived protrusion extends at the site of breach in an UNC-40 (netrin receptor) dependent manner (Hagedorn et al, 2013). UNC-40 is not required for invadopodia formation, indicating that invadopodia and the invasive protrusion are regulated distinctly (Morrissey et al, 2013). We hypothesized two possible mechanisms for expansion of the protrusion: redistribution of the plasma membrane, which would not yield an increase in AC size, or addition of new membrane, which would increase the size of the AC.…”

Section: Resultsmentioning

confidence: 99%

Cell Invasion In Vivo via Rapid Exocytosis of a Transient Lysosome-Derived Membrane Domain

et al. 2017

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Summary Invasive cells use small invadopodia to breach basement membrane (BM), a dense matrix that encases tissues. Following the breach, a large protrusion forms to clear a path for tissue entry by poorly understood mechanisms. Using RNAi screening for defects in C. elegans anchor cell (AC) invasion, we found that UNC-6(netrin)/UNC-40(DCC) signaling at the BM breach site directs exocytosis of lysosomes using the exocyst and SNARE SNAP-29 to form a large protrusion that invades vulval tissue. Live-cell imaging revealed that the protrusion is enriched in the matrix metalloprotease ZMP-1 and transiently expands AC volume more than 20%, displacing surrounding BM and vulval epithelium. Photobleaching and genetic perturbations showed that the BM receptor dystroglycan forms a membrane diffusion barrier at the neck of the protrusion that enables protrusion growth. Together these studies define a netrin dependent pathway that builds an invasive protrusion, an isolated lysosome-derived membrane structure specialized to breach tissue barriers.

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Section: Resultsmentioning

confidence: 99%

Cell Invasion In Vivo via Rapid Exocytosis of a Transient Lysosome-Derived Membrane Domain

et al. 2017

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“…It is expressed in most normal tissues, including the colonic mucosa, and its expression was greatly reduced or absent in most tested colorectal carcinomas [16]. DCC directs cell invasion through the basement membrane, an essential step in the pathological progression of human cancer [17]. Currently, DCC is known to be involved in the following biological processes: guidance of developing axons,4 induction of apoptosis [18], control of colorectal tumorigenesis [19], and angiogenesis [20].…”

Section: Discussionmentioning

confidence: 99%

Genetic association of deleted in colorectal carcinoma variants with breast cancer risk: A case-control study

Liu

Wang

et al. 2016

Oncotarget

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Deleted in colorectal carcinoma (DCC), a netrin-1 dependence receptor, is correlated with cell progression, migration, and adhesion. Evidence indicated that DCC was frequently down-regulated in many cancers. However, the association of DCC with breast cancer remains uncertain. We conducted a case-control study to investigate the impact of three DCC gene variants (rs2229080, rs7504990, and rs4078288) on breast cancer susceptibility in Chinese women. This study included 560 breast cancer patients and 583 age-matched healthy controls from Northwest China. The three gene variants were genotyped via Sequenom MassARRAY. Odds ratios (ORs) and 95% confidence intervals (CIs) were utilized to evaluate the associations. We found that individuals with the rs2229080 C/G, C/C, and C/G-CC genotypes had a higher breast cancer risk, and the minor allele C was associated with increased breast cancer risk in an allele model. We observed a significantly decreased breast cancer risk with the rs7504990 C/T, T/T, and C/T-T/T genotypes, and the minor allele T was protective against breast cancer in an allele model. In addition, rs2229080 was associated with the axillary lymph node (LN) metastasis status. An age-stratified analysis revealed an association between rs2229080 and reduced breast cancer risk among older patients (≥ 49 years). Furthermore, the haplotype analysis showed that the Crs2229080Crs7504990Ars4078288 haplotype was associated with a decreased breast cancer risk. However, the results indicated a lack of association between rs4078288 and breast cancer risk. These findings affirmed that rs2229080 and rs7504990 polymorphisms in DCC might be related with breast cancer susceptibility in Chinese women.

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“…The proposed regulatory role of small GTPases presented here also suggests that an outcome of the deregulated activity of small GTPases, which frequently occurs in tumor progression, can consequently result in deregulation of the Netrin receptors. Netrin receptor functions have been implicated in tumorigenic processes such as angiogenesis [ 42 , 43 ], apoptosis, and cell invasion [ 44 – 46 ], thus suggesting UNC-5 or UNC-40/DCC as targets for cancer therapy that might be less deleterious to normal cells than targeting small GTPases. Taken together, the data presented in this study identifies small GTPases as regulatory links allowing for cross talk between Wnt and Netrin signaling pathways, which play central roles in normal development and human disease.…”

Section: Discussionmentioning

confidence: 99%

The Wnt Frizzled Receptor MOM-5 Regulates the UNC-5 Netrin Receptor through Small GTPase-Dependent Signaling to Determine the Polarity of Migrating Cells

et al. 2015

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Wnt and Netrin signaling regulate diverse essential functions. Using a genetic approach combined with temporal gene expression analysis, we found a regulatory link between the Wnt receptor MOM-5/Frizzled and the UNC-6/Netrin receptor UNC-5. These two receptors play key roles in guiding cell and axon migrations, including the migration of the C. elegans Distal Tip Cells (DTCs). DTCs migrate post-embryonically in three sequential phases: in the first phase along the Antero-Posterior (A/P) axis, in the second, along the Dorso-Ventral (D/V) axis, and in the third, along the A/P axis. Loss of MOM-5/Frizzled function causes third phase A/P polarity reversals of the migrating DTCs. We show that an over-expression of UNC-5 causes similar DTC A/P polarity reversals and that unc-5 deficits markedly suppress the A/P polarity reversals caused by mutations in mom-5/frizzled. This implicates MOM-5/Frizzled as a negative regulator of unc-5. We provide further evidence that small GTPases mediate MOM-5’s regulation of unc-5 such that one outcome of impaired function of small GTPases like CED-10/Rac and MIG-2/RhoG is an increase in unc-5 function. The work presented here demonstrates the existence of cross talk between components of the Netrin and Wnt signaling pathways and provides further insights into the way guidance signaling mechanisms are integrated to orchestrate directed cell migration.

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Cell invasion through basement membrane

Cited by 25 publications

References 50 publications

Cell Invasion In Vivo via Rapid Exocytosis of a Transient Lysosome-Derived Membrane Domain

Cell Invasion In Vivo via Rapid Exocytosis of a Transient Lysosome-Derived Membrane Domain

Genetic association of deleted in colorectal carcinoma variants with breast cancer risk: A case-control study

The Wnt Frizzled Receptor MOM-5 Regulates the UNC-5 Netrin Receptor through Small GTPase-Dependent Signaling to Determine the Polarity of Migrating Cells

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