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Invadopodia

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https://www.readbyqxmd.com/read/28436416/lpp-is-a-src-substrate-required-for-invadopodia-formation-and-efficient-breast-cancer-lung-metastasis
#1
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
#2
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...
March 16, 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
#3
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...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412099/tumor-cell-invadopodia-invasive-protrusions-that-orchestrate-metastasis
#4
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-dlg5-regulates-hcc-invadopodia
#5
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 non-tumor tissues and liver cells. Lower Dlg5 expression was associated with advanced stages of HCC, and poor overall and disease-free survival of HCC patients...
April 8, 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
#6
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
#7
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
#8
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 EGF 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. We identified the Rho-family guanine nucleotide exchange factor (GEF) Vav2 in a comprehensive screen for human SH2 domains that bind selectively to phosphorylated cortactin...
March 29, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28301299/differential-role-for-pak1-and-pak4-during-the-invadopodia-lifecycle
#9
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 PDZRho-GEF. 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
#10
(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
#11
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
https://www.readbyqxmd.com/read/28247964/pi-3-4-p2-plays-critical-roles-in-the-regulation-of-focal-adhesion-dynamics-of-mda-mb-231-breast-cancer-cells
#12
Miki Fukumoto, Takeshi Ijuin, Tadaomi Takenawa
Phosphoinositides play pivotal roles in the regulation of cancer cell phenotypes. Among them, phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2 ) localizes to the invadopodia, and positively regulates tumor cell invasion. In this study, we examined the effect of PI(3,4)P2 on focal adhesion dynamics in MDA-MB-231 basal breast cancer cells. Knockdown of SHIP2, a phosphatidylinositol 3,4,5-trisphosphatase (PIP3 ) 5-phosphatase that generates PI(3,4)P2 , in MDA-MB-231 breast cancer cells, induced the development of focal adhesions and cell spreading, leading to the suppression of invasion...
March 1, 2017: Cancer Science
https://www.readbyqxmd.com/read/28235780/inhibitory-cortactin-nanobodies-delineate-the-role-of-nta-and-sh3-domain-specific-functions-during-invadopodium-formation-and-cancer-cell-invasion
#13
Laurence Bertier, Ciska Boucherie, Olivier Zwaenepoel, Berlinda Vanloo, Marleen Van Troys, Isabel Van Audenhove, Jan Gettemans
Cancer cells exploit different strategies to escape from the primary tumor, gain access to the circulation, disseminate throughout the body, and form metastases, the leading cause of death by cancer. Invadopodia, proteolytically active plasma membrane extensions, are essential in this escape mechanism. Cortactin is involved in every phase of invadopodia formation, and its overexpression is associated with increased invadopodia formation, extracellular matrix degradation, and cancer cell invasion. To analyze endogenous cortactin domain function in these processes, we characterized the effects of nanobodies that are specific for the N-terminal acidic domain of cortactin and expected to target small epitopes within this domain...
February 24, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28219404/erratum-to-cdc42-interacting-protein-4-promotes-metastasis-of-nasopharyngeal-carcinoma-by-mediating-invadopodia-formation-and-activating-egfr-signaling
#14
Dong-Fang Meng, Ping Xie, Li-Xia Peng, Rui Sun, Dong-Hua Luo, Qiu-Yan Chen, Xing Lv, Lin Wang, Ming-Yuan Chen, Hai-Qiang Mai, Ling Guo, Xiang Guo, Li-Sheng Zheng, Li Cao, Jun-Ping Yang, Meng-Yao Wang, Yan Mei, Yuan-Yuan Qiang, Zi-Meng Zhang, Jing-Ping Yun, Bi-Jun Huang, Chao-Nan Qian
No abstract text is available yet for this article.
February 20, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28202690/a-rhog-mediated-signaling-pathway-that-modulates-invadopodia-dynamics-in-breast-cancer-cells
#15
Silvia M Goicoechea, Ashtyn Zinn, Sahezeel S Awadia, Kyle Snyder, Rafael Garcia-Mata
One of the hallmarks of cancer is the ability of tumor cells to invade surrounding tissues and metastasize. During metastasis, cancer cells degrade the extracellular matrix, which acts as a physical barrier, by developing specialized actin-rich membrane protrusion structures called invadopodia. The formation of invadopodia is regulated by Rho GTPases, a family of proteins that regulates the actin cytoskeleton. Here, we describe a novel role for RhoG in the regulation of invadopodia disassembly in human breast cancer cells...
March 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28129778/cdc42-interacting-protein-4-promotes-metastasis-of-nasopharyngeal-carcinoma-by-mediating-invadopodia-formation-and-activating-egfr-signaling
#16
Dong-Fang Meng, Ping Xie, Li-Xia Peng, Rui Sun, Dong-Hua Luo, Qiu-Yan Chen, Xing Lv, Lin Wang, Ming-Yuan Chen, Hai-Qiang Mai, Ling Guo, Xiang Guo, Li-Sheng Zheng, Li Cao, Jun-Ping Yang, Meng-Yao Wang, Yan Mei, Yuan-Yuan Qiang, Zi-Meng Zhang, Jing-Ping Yun, Bi-Jun Huang, Chao-Nan Qian
BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common malignancy in Southern China and Southeast Asia. In this study, we investigated the functional and molecular mechanisms by which CDC42-interacting protein 4 (CIP4) influences NPC. METHODS: The expression levels of CIP4 were examined by Western blot, qRT-PCR or IHC. MTT assay was used to detect the proliferative rate of NPC cells. The invasive abilities were examined by matrigel and transwell assay. The metastatic abilities of NPC cells were revealed in BALB/c nude mice...
January 28, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28127051/ror2-signaling-regulates-golgi-structure-and-transport-through-ift20-for-tumor-invasiveness
#17
Michiru Nishita, Seung-Yeol Park, Tadashi Nishio, Koki Kamizaki, ZhiChao Wang, Kota Tamada, Toru Takumi, Ryuju Hashimoto, Hiroki Otani, Gregory J Pazour, Victor W Hsu, Yasuhiro Minami
Signaling through the Ror2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion. Here, we identify intraflagellar transport 20 (IFT20) as a new target of this signaling in tumors that lack primary cilia, and find that IFT20 mediates the ability of Ror2 signaling to induce the invasiveness of these tumors. We also find that IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex, which promotes Golgi ribbon formation in achieving polarized secretion for cell migration and invasion...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28098764/iqgap1-in-podosomes-invadosomes-is-involved-in-the-progression-of-glioblastoma-multiforme-depending-on-the-tumor-status
#18
Deborah Rotoli, Natalia Dolores Pérez-Rodríguez, Manuel Morales, María Del Carmen Maeso, Julio Ávila, Ali Mobasheri, Pablo Martín-Vasallo
Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor. GBM is formed by a very heterogeneous astrocyte population, neurons, neovascularization and infiltrating myeloid cells (microglia and monocyte derived macrophages). The IQGAP1 scaffold protein interacts with components of the cytoskeleton, cell adhesion molecules, and several signaling molecules to regulate cell morphology and motility, cell cycle and other cellular functions. IQGAP1 overexpression and delocalization has been observed in several tumors, suggesting a role for this protein in cell proliferation, transformation and invasion...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28094049/ep4-receptor-promotes-invadopodia-and-invasion-in-human-breast-cancer
#19
Felix Tönisen, Louisiane Perrin, Battuya Bayarmagnai, Koen van den Dries, Alessandra Cambi, Bojana Gligorijevic
The production of Prostaglandin E2 (PGE2) is elevated in human breast cancer cells. The abnormal expression of COX-2, which is involved in the synthesis of PGE2, was recently reported as a critical determinant for invasiveness of human breast cancer cells. Autocrine and paracrine PGE2-mediated stimulation of the PGE2 receptor EP4 transduces multiple signaling pathways leading to diverse patho-physiological effects, including tumor cell invasion and metastasis. It is known that PGE2-induced EP4 activation can transactivate the intracellular signaling pathway of the epidermal growth factor receptor (EGFR)...
March 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28076931/varying-effects-of-egf-hgf-and-tgf%C3%AE-on-formation-of-invadopodia-and-invasiveness-of-melanoma-cell-lines-of-different-origin
#20
A Makowiecka, A Simiczyjew, D Nowak, A J Mazur
The understanding of melanoma malignancy mechanisms is essential for patient survival, because melanoma is responsible for ca. 75% of deaths related to skin cancers. Enhanced formation of invadopodia and extracellular matrix (ECM) degradation are two important drivers of cell invasion, and actin dynamics facilitate protrusive activity by providing a driving force to push through the ECM. We focused on the influence of epidermal growth factor (EGF), hepatocyte growth factor (HGF) and transforming growth factor β (TGFβ) on melanoma cell invasiveness, since they are observed in the melanoma microenvironment...
December 9, 2016: European Journal of Histochemistry: EJH
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