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Invadopodia

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https://www.readbyqxmd.com/read/28804630/protected-cytoskeletal-related-proteins-towards-a-resolution-of-contradictions-regarding-the-role-of-the-cytoskeleton-in-cancer
#1
Daniel T Segarra, John M Yavorski, George Blanck
Initial reports of the role of the cytoskeleton in cancer indicated that tumor cells with a more disorganized cytoskeleton were more tumorigenic. These reports were based on stains for the F-actin cytoskeleton, for example, using phalloidin or anti-F-actin antibody reagents, and gave a basic impression of F-actin-based cytoskeletal integrity. Later developments emphasized the significance of the cytoskeletal elements in cell migration, presumably associated with either basement membrane invasion or metastasis, or both, with several specific proteins implicated in the formation of cell invadopodia...
August 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28798239/interaction-of-munc18c-and-syntaxin4-facilitates-invadopodium-formation-and-extracellular-matrix-invasion-of-tumour-cells
#2
Megan I Brasher, David M Martynowicz, Olivia R Grafinger, Andrea Hucik, Emma Shanks-Skinner, James Uniacke, Marc G Coppolino
Tumor cell invasion involves targeted localization of proteins required for interactions of the extracellular matrix (ECM) and for proteolysis. The localization of many proteins during these cell-ECM interactions relies on membrane trafficking mediated in part by soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The SNARE protein syntaxin4 (Stx4) is involved in the formation of invasive structures called invadopodia; however, it is unclear how Stx4 function is regulated during tumor cell invasion...
August 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28797528/actinin-1-and-actinin-4-play-essential-but-distinct-roles-in-invadopodia-formation-by-carcinoma-cells
#3
Hideki Yamaguchi, Yuumi Ito, Nami Miura, Yuko Nagamura, Ayaka Nakabo, Kiyoko Fukami, Kazufumi Honda, Ryuichi Sakai
Invadopodia are ventral membrane protrusions formed by cancer cells that degrade the extracellular matrix (ECM) during tumor invasion and metastasis. Formation of invadopodia is initiated by the assembly of actin filaments (F-actin) that results from the coordinated activation of several actin regulatory proteins. Actinin-1 and actinin-4 are actin bundling proteins expressed in non-muscle cells and actinin-4 is preferentially associated with malignant phenotypes of carcinoma cells. In this study, we investigated the role of actinin-1 and -4 in invadopodia formation...
August 1, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28783171/the-pdgfr%C3%AE-laminin-b1-keratin-19-cascade-drives-tumor-progression-at-the-invasive-front-of-human-hepatocellular-carcinoma
#4
O Govaere, M Petz, J Wouters, Y-P Vandewynckel, E J Scott, B Topal, F Nevens, C Verslype, Q M Anstee, H Van Vlierberghe, W Mikulits, T Roskams
Human hepatocellular carcinomas (HCCs) expressing the biliary/hepatic progenitor cell marker keratin 19 (K19) have been linked with a poor prognosis and exhibit an increase in platelet-derived growth factor receptor α (PDGFRα) and laminin beta 1 (LAMB1) expression. PDGFRα has been reported to induce de novo synthesis of LAMB1 protein in a Sjogren syndrome antigen B (La/SSB)-dependent manner in a murine metastasis model. However, the role of this cascade in human HCC remains unclear. This study focused on the functional role of the PDGFRα-La/SSB-LAMB1 pathway and its molecular link to K19 expression in human HCC...
August 7, 2017: Oncogene
https://www.readbyqxmd.com/read/28767724/%C3%AE-3-integrin-expression-is-required-for-invadopodia-mediated-ecm-degradation-in-lung-carcinoma-cells
#5
Rafael Peláez, Xabier Morales, Elizabeth Salvo, Saray Garasa, Carlos Ortiz de Solórzano, Alfredo Martínez, Ignacio M Larrayoz, Ana Rouzaut
Cancer related deaths are primarily due to tumor metastasis. To facilitate their dissemination to distant sites, cancer cells develop invadopodia, actin-rich protrusions capable of degrading the surrounding extracellular matrix (ECM). We aimed to determine whether β3 integrin participates in invadopodia formed by lung carcinoma cells, based on our previous findings of specific TGF-β induction of β3 integrin dependent metastasis in animal models of lung carcinoma. In this study, we demonstrate that lung carcinoma cells form invadopodia in response to TGF-β exposure...
2017: PloS One
https://www.readbyqxmd.com/read/28751006/apolipoprotein-e-promotes-invasion-in-oral-squamous-cell-carcinoma
#6
Sangeeta K Jayakar, Olivier Loudig, Margaret Brandwein-Gensler, Ryung S Kim, Thomas J Ow, Berrin Ustun, Thomas M Harris, Michael B Prystowsky, Geoffrey Childs, Jeffrey E Segall, Thomas J Belbin
Oral squamous cell carcinoma (OSCC) patients generally have a poor prognosis, due to the invasive nature of these tumors. In comparing transcription profiles between OSCC tumors with a more invasive (WPOI 5) versus a less invasive (WPOI 3) pattern of invasion, we identified a total of 97 genes that were overexpressed at least 1.5-fold in the more invasive tumor subtype. The most functionally relevant genes were assessed using in vitro invasion assays with an OSCC cell line (UM-SCC-1). Individual siRNA knockdown of 15 of these 45 genes resulted in significant reductions in tumor cell invasion compared to a non-targeting siRNA control...
July 24, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28743828/tm4sf5-promotes-metastatic-behavior-of-cells-in-3d-extracellular-matrix-gels-by-reducing-dependency-on-environmental-cues
#7
Dae-Geun Song, Gyu-Ho Lee, Seo Hee Nam, Jin-Gyu Cheong, Doyoung Jeong, Seo-Jin Lee, Cheol-Ho Pan, Jae Woo Jung, Hye-Jin Kim, Jihye Ryu, Ji Eon Kim, Somi Kim, Chang Yun Cho, Min-Kyung Kang, Kyung-Min Lee, Jung Weon Lee
Transmembrane 4 L six family member 5 (TM4SF5) is highly expressed in hepatocellular carcinoma tissues and enhances migration in two-dimensional environments. Here, we investigated how TM4SF5 is involved in diverse pro-metastatic phenotypes in in vivo-like three-dimensional (3D) extracellular matrix gels. TM4SF5-positive cells aggressively formed invasive foci in 3D Matrigel, depending on TM4SF5-mediated signaling activity, cytoskeletal organization, and matrix metallopeptidase (MMP) 2-mediated extracellular remodeling, whereas TM4SF5-null cells did not...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28730229/molecular-analysis-of-brca1-and-brca2-genes-by-next-generation-sequencing-and-ultrastructural-aspects-of-breast-tumor-tissue
#8
Corina Elena Mihalcea, Ana Maria Moroşanu, Daniela Murăraşu, Liliana Puiu, Sabin Aurel Cinca, Silviu Cristian Voinea, Nicolae Mirancea
In this paper, we focus our interest on the dynamics alterations of the tumor-stroma interface at the ultrastructural level and to detect BRCA1 and BRCA2 mutations using next generation sequencing (NGS) of breast tumor tissue. Electron microscopic investigation revealed some peculiar infrastructural alterations of the tumor cells per se as well as of the tumor-stroma interface: invadopodia, shedding microvesicles, altered morphology and reduced number of telocytes, different abnormalities of the microvasculature...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/28692057/the-interactome-of-metabolic-enzyme-carbonic-anhydrase-ix-reveals-novel-roles-in-tumor-cell-migration-and-invadopodia-mmp14-mediated-invasion
#9
M Swayampakula, P C McDonald, M Vallejo, E Coyaud, S C Chafe, A Westerback, G Venkateswaran, J Shankar, G Gao, E M N Laurent, Y Lou, K L Bennewith, C T Supuran, I R Nabi, B Raught, S Dedhar
Carbonic anhydrase IX (CAIX) is a hypoxia inducible factor 1-induced, cell surface pH regulating enzyme with an established role in tumor progression and clinical outcome. However, the molecular basis of CAIX-mediated tumor progression remains unclear. Here, we have utilized proximity dependent biotinylation (BioID) to map the CAIX 'interactome' in breast cancer cells in order to identify physiologically relevant CAIX-associating proteins with potential roles in tumor progression. High confidence proteins identified include metabolic transporters, β1 integrins, integrin-associated protein CD98hc and matrix metalloprotease 14 (MMP14)...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28654281/differential-depth-sensing-reduces-cancer-cell-proliferation-via-rho-rac-regulated-invadopodia
#10
Parthiv Kant Chaudhuri, Catherine Qiurong Pan, Boon Chuan Low, Chwee Teck Lim
Bone, which is composed of a porous matrix, is one of the principal secondary locations for cancer. However, little is known about the effect of this porous microenvironment in regulating cancer cell proliferation. Here, we examine how the depth of the pores can transduce a mechanical signal and reduce the proliferation of noncancer breast epithelial cells (MCF-10A) and malignant breast cancer cells (MDA-MB-231 and MCF-7) using micrometer-scale topographic features. Interestingly, cells extend actin-rich protrusions, such as invadopodia, to sense the depth of the matrix pore and activate actomyosin contractility to decrease MCF-10A proliferation...
July 25, 2017: ACS Nano
https://www.readbyqxmd.com/read/28644148/5-azacytidine-promotes-invadopodia-formation-and-tumor-metastasis-through-the-upregulation-of-pi3k-in-ovarian-cancer-cells
#11
Dan Cao, Dan Li, Yong Huang, Yu Ma, Binglan Zhang, Chengjian Zhao, Senyi Deng, Min Luo, Tao Yin, Yu-Quan Wei, Wei Wang
The high incidence of metastasis accounts for most of the lethality of ovarian cancer. Invadopodia are small, specialized types of machinery that degrade the extracellular matrix and are thus involved in the invasion and metastasis of cancer cells. The formation of invadopodia is regulated by both genetic and epigenetic factors. However, the ways by which methylation/demethylation regulates the dynamics of invadopodia in ovarian cancer are largely unknown. In this study, we found that the inhibition of methylation by 5-AZ (5-Azacytidine) increased the formation of invadopodia and enhanced degradation of the extracellular matrix in ovarian cancer cells...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28569910/cations-induce-shape-remodeling-of-negatively-charged-phospholipid-membranes
#12
Z T Graber, Z Shi, T Baumgart
The divalent cation Ca(2+) is a key component in many cell signaling and membrane trafficking pathways. Ca(2+) signal transduction commonly occurs through interaction with protein partners. However, in this study we show a novel mechanism by which Ca(2+) may impact membrane structure. We find an asymmetric concentration of Ca(2+) across the membrane triggers deformation of membranes containing negatively charged lipids such as phosphatidylserine (PS) and phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2). Membrane invaginations in vesicles were observed forming away from the leaflet with higher Ca(2+) concentration, showing that Ca(2+) induces negative curvature...
June 14, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28548369/invadosomes-are-coming-new-insights-into-function-and-disease-relevance
#13
REVIEW
Elyse K Paterson, Sara A Courtneidge
Invadopodia and podosomes are discrete, actin-based molecular protrusions that form in cancer cells and normal cells, respectively, in response to diverse signaling pathways and extracellular matrix cues. Although they participate in a host of different cellular processes, they share a common functional theme of controlling pericellular proteolytic activity, which sets them apart from other structures that function in migration and adhesion, including focal adhesions, lamellipodia, and filopodia. In this review, we highlight research that explores the function of these complex structures, including roles for podosomes in embryonic and postnatal development, in angiogenesis and remodeling of the vasculature, in maturation of the postsynaptic membrane, in antigen sampling and recognition, and in cell-cell fusion mechanisms, as well as the involvement of invadopodia at multiple steps of the metastatic cascade, and how all of this may apply in the treatment of human disease states...
May 26, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28498365/inhibition-of-twist1-mediated-invasion-by-chk2-promotes-premature-senescence-in-p53-defective-cancer-cells
#14
Debasis Nayak, Anmol Kumar, Souneek Chakraborty, Reyaz Ur Rasool, Hina Amin, Archana Katoch, Veena Gopinath, Vidushi Mahajan, Mahesh K Zilla, Bilal Rah, Sumit G Gandhi, Asif Ali, Lekha Dinesh Kumar, Anindya Goswami
Twist1, a basic helix-loop-helix transcription factor is implicated as a key mediator of epithelial-mesenchymal transition (EMT) and metastatic dissemination in p53-deficient cancer cells. On the other hand, checkpoint kinase 2 (Chk2), a major cell cycle regulatory protein provides a barrier to tumorigenesis due to DNA damage response by preserving genomic stability of the cells. Here we demonstrate that Chk2 induction proficiently abrogates invasion, cell scattering and invadopodia formation ability of p53-mutated invasive cells by suppressing Twist1, indicating Chk2 confers vital role in metastasis prevention...
May 12, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28468988/adam12-induction-by-twist1-promotes-tumor-invasion-and-metastasis-via-regulation-of-invadopodia-and-focal-adhesions
#15
Mark A Eckert, Miguel Santiago-Medina, Thinzar M Lwin, Jihoon Kim, Sara A Courtneidge, Jing Yang
The Twist1 transcription factor promotes tumor invasion and metastasis by inducing epithelial-mesenchymal transition (EMT) and invadopodia-mediated extracellular matrix (ECM) degradation. The critical transcription targets of Twist1 for mediating these events remain to be uncovered. Here, we report that Twist1 strongly induces expression of a disintegrin and metalloproteinase 12 (ADAM12). We observed that the expression levels of Twist1 mRNA and ADAM12 mRNA are tightly correlated in human breast tumors. Knocking down ADAM12 blocked cell invasion in a 3D mammary organoid culture...
June 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28446539/transient-mechanical-strain-promotes-the-maturation-of-invadopodia-and-enhances-cancer-cell-invasion-in-vitro
#16
Alexander N Gasparski, Snehal Ozarkar, Karen A Beningo
Cancer cell invasion is influenced by various biomechanical forces found within the microenvironment. We have previously found that invasion is enhanced in fibrosarcoma cells when transient mechanical stimulation is applied within an in vitro mechano-invasion assay. This enhancement of invasion is dependent on cofilin, a known regulator of invadopodia maturation. Invadopodia are actin-rich structures present in invasive cancer cells that are enzymatically active and degrade the surrounding extracellular matrix to facilitate invasion...
April 26, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28436416/lpp-is-a-src-substrate-required-for-invadopodia-formation-and-efficient-breast-cancer-lung-metastasis
#17
Elaine Ngan, Konstantin Stoletov, Harvey W Smith, Jessica Common, William J Muller, John D Lewis, Peter M Siegel
We have previously shown that lipoma preferred partner (LPP) mediates TGFβ-induced breast cancer cell migration and invasion. Herein, we demonstrate that diminished LPP expression reduces circulating tumour cell numbers, impairs cancer cell extravasation and diminishes lung metastasis. LPP localizes to invadopodia, along with Tks5/actin, at sites of matrix degradation and at the tips of extravasating breast cancer cells as revealed by intravital imaging of the chick chorioallantoic membrane (CAM). Invadopodia formation, breast cancer cell extravasation and metastasis require an intact LPP LIM domain and the ability of LPP to interact with α-actinin...
April 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/28415794/micrornas-of-the-mir-17-92-cluster-regulate-multiple-aspects-of-pancreatic-tumor-development-and-progression
#18
Brian Quattrochi, Anushree Gulvady, David R Driscoll, Makoto Sano, David S Klimstra, Christopher E Turner, Brian C Lewis
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy characterized by resistance to currently employed chemotherapeutic approaches. Members of the mir-17~92 cluster of microRNAs (miRNAs) are upregulated in PDAC, but the precise roles of these miRNAs in PDAC are unknown. Using genetically engineered mouse models, we show that loss of mir-17~92 reduces ERK pathway activation downstream of mutant KRAS and promotes the regression of KRASG12D-driven precursor pancreatic intraepithelial neoplasias (PanINs) and their replacement by normal exocrine tissue...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415608/collagen-type-iv-alpha-1-col4a1-and-collagen-type-xiii-alpha-1-col13a1-produced-in-cancer-cells-promote-tumor-budding-at-the-invasion-front-in-human-urothelial-carcinoma-of-the-bladder
#19
Makito Miyake, Shunta Hori, Yosuke Morizawa, Yoshihiro Tatsumi, Michihiro Toritsuka, Sayuri Ohnishi, Keiji Shimada, Hideki Furuya, Vedbar S Khadka, Youping Deng, Kenta Ohnishi, Kota Iida, Daisuke Gotoh, Yasushi Nakai, Takeshi Inoue, Satoshi Anai, Kazumasa Torimoto, Katsuya Aoki, Nobumichi Tanaka, Noboru Konishi, Kiyohide Fujimoto
Current knowledge of the molecular mechanism driving tumor budding is limited. Here, we focused on elucidating the detailed mechanism underlying tumor budding in urothelial cancer of the bladder. Invasive urothelial cancer was pathologically classified into three groups as follows: nodular, trabecular, and infiltrative (tumor budding). Pathohistological analysis of the orthotopic tumor model revealed that human urothelial cancer cell lines MGH-U3, UM-UC-14, and UM-UC-3 displayed typical nodular, trabecular, and infiltrative patterns, respectively...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412099/tumor-cell-invadopodia-invasive-protrusions-that-orchestrate-metastasis
#20
REVIEW
Robert J Eddy, Maxwell D Weidmann, Ved P Sharma, John S Condeelis
Invadopodia are a subset of invadosomes that are implicated in the integration of signals from the tumor microenvironment to support tumor cell invasion and dissemination. Recent progress has begun to define how tumor cells regulate the plasticity necessary for invadopodia to assemble and function efficiently in the different microenvironments encountered during dissemination in vivo. Exquisite mapping by many laboratories of the pathways involved in integrating diverse invadopodium initiation signals, from growth factors, to extracellular matrix (ECM) and cell-cell contact in the tumor microenvironment, has led to insight into the molecular basis of this plasticity...
August 2017: Trends in Cell Biology
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