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Invadopodia

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https://www.readbyqxmd.com/read/28730229/molecular-analysis-of-brca1-and-brca2-genes-by-next-generation-sequencing-and-ultrastructural-aspects-of-breast-tumor-tissue
#1
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
#2
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
#3
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 examined how the depth of the pores could transduce a mechanical signal and reduce the proliferation of non-cancer breast epithelial cells (MCF-10A) and malignant breast cancer cells (MDA-MB-231 and MCF-7) using micron-scale topographic features. Interestingly, cells extended actin-rich protrusions, such as invadopodia to sense the depth of the matrix pore and activate actomyosin contractility to decrease MCF-10A proliferation...
June 27, 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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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...
April 12, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28390157/discs-large-homolog-5-decreases-formation-and-function-of-invadopodia-in-human-hepatocellular-carcinoma-via-girdin-and-tks5
#14
Yang Ke, Tianhao Bao, Qixin Zhou, Yan Wang, Jiayun Ge, Bimang Fu, Xuesong Wu, Haoran Tang, Zhitian Shi, Xuefen Lei, Cheng Zhang, Yuqi Tan, Haotian Chen, Zhitang Guo, Lin Wang
Invadopodium formation is a crucial early event of invasion and metastasis of hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying regulation of invadopodia remain elusive. This study aimed to investigate the potential role of discs large homolog 5 (Dlg5) in invadopodium formation and function in HCC. We found that Dlg5 expression was significantly lower in human HCC tissues and cell lines than adjacent nontumor tissues and liver cells. Lower Dlg5 expression was associated with advanced stages of HCC, and poor overall and disease-free survival of HCC patients...
July 15, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28381343/podoplanin-expression-in-peritumoral-keratinocytes-predicts-aggressive-behavior-in-extramammary-paget-s-disease
#15
Zaigen Cho, Eiichi Konishi, Mai Kanemaru, Taro Isohisa, Takahiro Arita, Minako Kawai, Miho Tsutsumi, Hiromi Mizutani, Hideya Takenaka, Toshiyuki Ozawa, Daisuke Tsuruta, Norito Katoh, Jun Asai
BACKGROUND: Recent studies have demonstrated podoplanin expression in several tumors, which has been associated with lymph node metastasis and poor prognosis. Podoplanin expression in peritumoral cells such as cancer-associated fibroblasts also correlates with tumor progression in several cancers. However, podoplanin expression and its association with extramammary Paget's disease (EMPD) remain unclear. OBJECTIVE: In this study, we examined whether the presence of podoplanin expression in tumor cells or peritumoral basal keratinocytes correlated with aggressive behavior in patients with EMPD and investigated the mechanisms of podoplanin-mediated tumor invasion in this disorder...
March 27, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28368050/tm4sf1-promotes-metastasis-of-pancreatic-cancer-via-regulating-the-expression-of-ddr1
#16
Jia-Chun Yang, Yi Zhang, Si-Jia He, Ming-Ming Li, Xiao-Lei Cai, Hui Wang, Lei-Ming Xu, Jia Cao
Transmembrane-4-L-six-family-1(TM4SF1), a four-transmembrane L6 family member, is highly expressed in various pancreatic cancer cell lines and promotes cancer cells metastasis. However, the TM4SF1-associated signaling network in metastasis remains unknown. In the present study, we found that TM4SF1 affected the formation and function of invadopodia. Silencing of TM4SF1 reduced the expression of DDR1 significantly in PANC-1 and AsPC-1 cells. Through double fluorescence immuno-staining and Co-immunoprecipitation, we also found that TM4SF1 colocalized with DDR1 and had an interaction with DDR1...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28356423/phosphorylated-cortactin-recruits-vav2-guanine-nucleotide-exchange-factor-to-activate-rac3-and-promote-invadopodial-function-in-invasive-breast-cancer-cells
#17
Brian J Rosenberg, Hava Gil-Henn, Christopher C Mader, Tiffany Halo, Taofei Yin, John Condeelis, Kazuya Machida, Yi I Wu, Anthony J Koleske
Breast carcinoma cells use specialized, actin-rich protrusions called invadopodia to degrade and invade through the extracellular matrix. Phosphorylation of the actin nucleation-promoting factor and actin-stabilizing protein cortactin downstream of the epidermal growth factor receptor-Src-Arg kinase cascade is known to be a critical trigger for invadopodium maturation and subsequent cell invasion in breast cancer cells. The functions of cortactin phosphorylation in this process, however, are not completely understood...
May 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28301299/differential-role-for-pak1-and-pak4-during-the-invadopodia-lifecycle
#18
Nicole S Nicholas, Aikaterini Pipili, Michaela S Lesjak, Claire M Wells
PAK1 and PAK4 are members of the p-21 activated kinase family of serine/threonine kinases. PAK1 has previously been implicated in both the formation and disassembly of invasive cell protrusions, termed invadopodia. We recently reported a novel role for PAK4 during invadopodia maturation and confirmed a specific role for PAK1 in invadopodia formation; findings we will review here. Moreover, we found that PAK4 induction of maturation is delivered via interaction with the RhoA regulator PDZ-RhoGEF. We can now reveal that loss of PAK4 expression leads to changes in invadopodia dynamics...
March 16, 2017: Small GTPases
https://www.readbyqxmd.com/read/28298616/rhog-helps-to-disassemble-invadopodia-in-breast-cancer
#19
(no author information available yet)
No abstract text is available yet for this article.
March 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28287395/p27-kip1-promotes-invadopodia-turnover-and-invasion-through-the-regulation-of-the-pak1-cortactin-pathway
#20
Pauline Jeannot, Ada Nowosad, Renaud T Perchey, Caroline Callot, Evangeline Bennana, Takanori Katsube, Patrick Mayeux, François Guillonneau, Stéphane Manenti, Arnaud Besson
p27(Kip1) (p27) is a cyclin-CDK inhibitor and negative regulator of cell proliferation. p27 also controls other cellular processes including migration and cytoplasmic p27 can act as an oncogene. Furthermore, cytoplasmic p27 promotes invasion and metastasis, in part by promoting epithelial to mesenchymal transition. Herein, we find that p27 promotes cell invasion by binding to and regulating the activity of Cortactin, a critical regulator of invadopodia formation. p27 localizes to invadopodia and limits their number and activity...
March 13, 2017: ELife
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