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kindlin-2

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https://www.readbyqxmd.com/read/28969700/kindlin-2-promotes-hepatocellular-carcinoma-invasion-and-metastasis-by-increasing-wnt-%C3%AE-catenin-signaling
#1
Jie Lin, Wansong Lin, Yunbin Ye, Liping Wang, Xiaoyan Chen, Shengbing Zang, Aimin Huang
BACKGROUND: Kindlin-2 is a member of the focal adhesion protein family that regulates invasion and metastasis in multiple malignancies; however, little is known about the role of Kindlin-2 in hepatocellular carcinoma (HCC) progression. METHODS: Immunohistochemistry was used to investigate Kindlin-2 expression in 177 pairs of human HCC and adjacent liver tissue samples. The role of Kindlin-2 in the in vitro invasion and migration of HCC cell lines was evaluated in MHCC97H, LM3 and SMMC7721 cells...
September 29, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28912124/kindlin-2-recruits-paxillin-and-arp2-3-to-promote-membrane-protrusions-during-initial-cell-spreading
#2
Ralph T Böttcher, Maik Veelders, Pascaline Rombaut, Jan Faix, Marina Theodosiou, Theresa E Stradal, Klemens Rottner, Roy Zent, Franz Herzog, Reinhard Fässler
Cell spreading requires the coupling of actin-driven membrane protrusion and integrin-mediated adhesion to the extracellular matrix. The integrin-activating adaptor protein kindlin-2 plays a central role for cell adhesion and membrane protrusion by directly binding and recruiting paxillin to nascent adhesions. Here, we report that kindlin-2 has a dual role during initial cell spreading: it binds paxillin via the pleckstrin homology and F0 domains to activate Rac1, and it directly associates with the Arp2/3 complex to induce Rac1-mediated membrane protrusions...
November 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28881595/effects-of-increased-kindlin-2-expression-in-bladder-cancer-stromal-fibroblasts
#3
Jitao Wu, Cuicui Yu, Li Cai, Youyi Lu, Lei Jiang, Chu Liu, Yongwei Li, Fan Feng, Zhenli Gao, Zhe Zhu, Shengqiang Yu, Hejia Yuan, Yuanshan Cui
Kindlin-2 is a focal adhesion protein highly expressed in bladder cancer stromal fibroblasts. We investigated the prognostic significance of Kindlin-2 in bladder cancer stromal fibroblasts and evaluated the effects of Kindlin-2 on the malignant behaviors of tumor cells. Immunohistochemical staining of 203 paraffin-embedded bladder cancer tissues showed that Kindlin-2 expression correlated with advanced stage, high grade, and relapse of bladder cancer. Kaplan-Meier survival analysis demonstrated that patients exhibiting high Kindlin-2 expression had shorter survival times than those with low Kindlin-2 expression (p < 0...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28864764/optogenetic-interrogation-of-integrin-%C3%AE-v%C3%AE-3-function-in-endothelial-cells
#4
Zhongji Liao, Ana Kasirer-Friede, Sanford J Shattil
αVβ3 is reported to promote angiogenesis in some model systems but not in others. Here we used optogenetics to study effects of αVβ3 interaction with the intracellular adapter, kindlin-2, on endothelial cell functions potentially relevant to angiogenesis. Since interaction of kindlin-2 with αVβ3 requires the C-terminal three residues of the β3 cytoplasmic tail (Arg-Gly-Thr; RGT), optogenetic probes LOVpep and ePDZ1 were fused to β3ΔRGT-GFP and mCherry-kindlin2, respectively, and expressed in β3-null microvascular endothelial cells...
September 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28833162/the-kindlin-2-double-act
#5
Xi Ye, Kim A Dora
No abstract text is available yet for this article.
October 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28799653/kindlin-2-interacts-with-endothelial-adherens-junctions-to-support-vascular-barrier-integrity
#6
Elzbieta Pluskota, Kamila M Bledzka, Katarzyna Bialkowska, Dorota Szpak, Dmitry A Soloviev, Sidney V Jones, Dmitriy Verbovetskiy, Edward F Plow
KEY POINTS: A reduction in Kindlin-2 levels in endothelial cells compromises vascular barrier function. Kindlin-2 is a previously unrecognized component of endothelial adherens junctions. By interacting directly and simultaneously with β- or γ-catenin and cortical actin filaments, Kindlin-2 stabilizes adherens junctions. The Kindlin-2 binding sites for β- and γ-catenin reside within its F1 and F3 subdomains. Although Kindlin-2 does not associate directly with tight junctions, its downregulation also destabilizes these junctions...
October 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28775002/kindlin-2-association-with-rho-gdp-dissociation-inhibitor-%C3%AE-suppresses-rac1-activation-and-podocyte-injury
#7
Ying Sun, Chen Guo, Ping Ma, Yumei Lai, Fan Yang, Jun Cai, Zhehao Cheng, Kuo Zhang, Zhongzhen Liu, Yeteng Tian, Yue Sheng, Ruijun Tian, Yi Deng, Guozhi Xiao, Chuanyue Wu
Alteration of podocyte behavior is critically involved in the development and progression of many forms of human glomerular diseases. The molecular mechanisms that control podocyte behavior, however, are not well understood. Here, we investigated the role of Kindlin-2, a component of cell-matrix adhesions, in podocyte behavior in vivo Ablation of Kindlin-2 in podocytes resulted in alteration of actin cytoskeletal organization, reduction of the levels of slit diaphragm proteins, effacement of podocyte foot processes, and ultimately massive proteinuria and death due to kidney failure...
August 3, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28755003/kindlin-2-could-influence-breast-nodule-elasticity-and-improve-lymph-node-metastasis-in-invasive-breast-cancer
#8
Xiaowei Xue, Junlai Li, Wenbo Wan, Xianquan Shi, Yiqiong Zheng
This study investigated the relationship between quantitative parameters of shear wave elastography (SWE, maximum elasticity [Emax], minimum elasticity [Emin], mean elasticity [Emean]), collagen intensity and Kindlin-2 expression in benign and malignant breast nodules, and if Kindlin-2 expression is related with lymph node metastasis. A total of 102 breast nodules from 102 patients were included in our study who underwent ultrasound elastography before surgery or core needle biopsy. There was a significant difference between benign and malignant breast nodules in Emax, Emean, collagen intensity and Kindlin-2 expression, but it had no difference in Emin...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28687620/kindlin-2-regulates-the-growth-of-breast-cancer-tumors-by-activating-csf-1-mediated-macrophage-infiltration
#9
Khalid Sossey-Alaoui, Elzbieta Pluskota, Katarzyna Bialkowska, Dorota Szpak, Yvonne Parker, Chevaun D Morrison, Daniel J Lindner, William P Schiemann, Edward F Plow
Interplay between tumor cells and host cells in the tumor microenvironment dictates the development of all cancers. In breast cancer, malignant cells educate host macrophages to adopt a protumorigenic phenotype. In this study, we show how the integrin-regulatory protein kindlin-2 (FERMT2) promotes metastatic progression of breast cancer through the recruitment and subversion of host macrophages. Kindlin-2 expression was elevated in breast cancer biopsy tissues where its levels correlated with reduced patient survival...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28677779/kindlin%C3%A2-2-promotes-clear-cell-renal-cell-carcinoma-progression-through-the-wnt-signaling-pathway
#10
Muhan Li, Xuelian Pei, Guoliang Wang, Jun Zhan, Juan Du, Hao Jiang, Yan Tang, Hongquan Zhang, Huiying He
Kindlin‑2 is an integrin-interacting, FERM-domain containing protein, which plays a critical role in tumor progression. However, the specific role of Kindlin‑2 in renal cell carcinoma (RCC) progression has not been described. In this study we investigated the role of Kindlin‑2 in progression of clear cell RCC (CCRCC), which is the most common RCC subtype, and its underlying mechanisms. Immunohistochemistry studies show that expression of Kindlin‑2 in CCRCC is positively correlated with tumor grade, and Kindlin‑2 expression in advanced CCRCC with lymph node metastasis was greater than in localized CCRCC...
July 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28667517/differential-expression-of-kindlin-1-and-kindlin-2-correlates-with-esophageal-cancer-progression-and-epidemiology
#11
Peng Wang, Jun Zhan, Jiagui Song, Yunling Wang, Weigang Fang, Zhihua Liu, Hongquan Zhang
Esophageal cancer (EC) is one of the most lethal malignancies in China, but the etiology and risk factors remain unclear. The integrin-interacting proteins Kindlin-1 and Kindlin-2 are focal adhesion molecules that activate transmembrane receptor integrins and regulate tumor cell growth, invasion, and metastasis. Here, we report that Kindlin-1 and Kindlin-2 are differentially expressed among Chinese EC patients. For this, Kindlin-1 and Kindlin-2 expression was evaluated in 220 EC patients by immunohistochemistry (IHC) and found to be correlated with the EC progression, along with a variety of epidemiologic parameters, including smoking, family EC history, and EC invasion status...
June 29, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28652408/the-extreme-c-terminal-region-of-kindlin-2-is-critical-to-its-regulation-of-integrin-activation
#12
Jamila Hirbawi, Katarzyna Bialkowska, Kamila M Bledzka, Jianmin Liu, Koichi Fukuda, Jun Qin, Edward F Plow
Kindlin-2 (K2), a 4.1R-ezrin-radixin-moesin (FERM) domain adaptor protein, mediates numerous cellular responses, including integrin activation. The C-terminal 15-amino acid sequence of K2 is remarkably conserved across species but is absent in canonical FERM proteins, including talin. In CHO cells expressing integrin αIIbβ3, co-expression of K2 with talin head domain resulted in robust integrin activation, but this co-activation was lost after deletion of as few as seven amino acids from the K2 C terminus...
August 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28640252/long-non-coding-rna-atb-promotes-malignancy-of-esophageal-squamous-cell-carcinoma-by-regulating-mir-200b-kindlin-2-axis
#13
Zhongwen Li, Xiaoliang Wu, Ling Gu, Qi Shen, Wen Luo, Chuangzhong Deng, Qianghua Zhou, Xinru Chen, Yanjie Li, ZuanFu Lim, Xing Wang, Jiahong Wang, Xianzi Yang
Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer-related death, especially in China. In addition, the prognosis of late stage patients is extremely poor. However, the biological significance of the long non-coding RNA lnc-ATB and its potential role in ESCC remain to be documented. In this study, we investigated the role of lnc-ATB and the underlying mechanism promoting its oncogenic activity in ESCC. Expression of lnc-ATB was higher in ESCC tissues and cell lines than that in normal counterparts...
June 22, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28454096/effects-of-increased-kindlin-2-expression-in-bladder-cancer-stromal-fibroblasts
#14
Jitao Wu, Cuicui Yu, Li Cai, Youyi Lu, Lei Jiang, Chu Liu, Yongwei Li, Fan Feng, Zhenli Gao, Zhe Zhu, Shengqiang Yu, Hejia Yuan, Yuanshan Cui
Kindlin-2 is a focal adhesion protein highly expressed in bladder cancer stromal fibroblasts. We investigated the prognostic significance of Kindlin-2 in bladder cancer stromal fibroblasts and evaluated the effects of Kindlin-2 on the malignant behaviors of tumor cells. Immunohistochemical staining of 203 paraffin-embedded bladder cancer tissues showed that Kindlin-2 expression correlated with advanced stage, high grade, and relapse of bladder cancer. Kaplan-Meier survival analysis demonstrated that patients exhibiting high Kindlin-2 expression had shorter survival times than those with low Kindlin-2 expression (p < 0...
April 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408404/smurf1-inhibits-integrin-activation-by-controlling-kindlin-2-ubiquitination-and-degradation
#15
Xiaofan Wei, Xiang Wang, Jun Zhan, Yuhan Chen, Weigang Fang, Lingqiang Zhang, Hongquan Zhang
Integrin activation is an indispensable step for various integrin-mediated biological functions. Kindlin-2 is known to coactivate integrins with Talin; however, molecules that restrict integrin activation are elusive. Here, we demonstrate that the E3 ubiquitin ligase Smurf1 controls the amount of Kindlin-2 protein in cells and hinders integrin activation. Smurf1 interacts with and promotes Kindlin-2 ubiquitination and degradation. Smurf1 selectively mediates degradation of Kindlin-2 but not Talin, leading to inhibition of αIIbβ3 integrin activation in Chinese hamster ovary cells and β1 integrin activation in fibroblasts...
May 1, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28223823/prognostic-implications-of-kindlin-proteins-in-human-osteosarcoma
#16
Kai Ning, Haoshaqiang Zhang, Zhigang Wang, Kun Li
The Kindlin protein family, comprising Kindlin-1, Kindlin-2 and Kindlin-3, play important roles in various human cancers. Here, to explore the clinical significance of Kindlins in human osteosarcomas, quantitative real-time PCR and Western blot analyses were performed to detect the expression of Kindlin-1, Kindlin-2 and Kindlin-3 mRNAs and proteins in 20 self-pairs of osteosarcoma and adjacent noncancerous tissues. Then, immunohistochemistry was performed to examine subcellular localizations and expression patterns of Kindlin proteins in 100 osteosarcoma and matched adjacent noncancerous tissues...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28163724/kindlin-2-modulates-the-survival-differentiation-and-migration-of-induced-pluripotent-cell-derived-mesenchymal-stromal-cells
#17
Mohsen Moslem, Reto Eggenschwiler, Christian Wichmann, Raymund Buhmann, Tobias Cantz, Reinhard Henschler
Kindlin-2 is a multidomain intracellular protein that can be recruited to β-integrin domains to activate signaling, initiate transcriptional programs, and bind to E-cadherin. To explore its involvement in cell fate decisions in mesenchymal cells, we studied the effects of Kindlin-2 modification (overexpression/knockdown) in induced pluripotent cell-derived mesenchymal stromal cells (iPSC-MSCs). Kindlin-2 overexpression resulted in increased proliferation and reduced apoptosis of iPSC-MSCs, as well as inhibition of their differentiation towards osteocytes, adipocytes, and chondrocytes...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28093281/kindlin-2-in-pancreatic-stellate-cells-promotes-the-progression-of-pancreatic-cancer
#18
Naoki Yoshida, Atsushi Masamune, Shin Hamada, Kazuhiro Kikuta, Tetsuya Takikawa, Fuyuhiko Motoi, Michiaki Unno, Tooru Shimosegawa
Pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis associated with pancreatic ductal adenocarcinoma (PDAC). Kindlin-2 is a focal adhesion protein that regulates the activation of integrins. This study aimed to clarify the role of kindlin-2 in PSCs in pancreatic cancer. Kindlin-2 expression in 79 resected pancreatic cancer tissues was examined by immunohistochemical staining. Kindlin-2-knockdown immortalized human PSCs were established using small interfering RNA. Pancreatic cancer cells were treated with conditioned media of PSCs, and the cell proliferation and migration were examined...
April 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27798104/uv-b-induced-cutaneous-inflammation-and-prospects-for-antioxidant-treatment-in-kindler-syndrome
#19
Kristin Maier, Yinghong He, Ute Wölfle, Philipp R Esser, Tilman Brummer, Christoph Schempp, Leena Bruckner-Tuderman, Cristina Has
Kindler syndrome (KS), a rare, autosomal recessive disorder comprises mechanical skin fragility and photosensitivity, which manifest early in life. The progression of the disorder is irreversible and results in tissue damage in form of cutaneous and mucosal atrophy and scarring and epithelial cancers. Here, we unravel molecular mechanisms of increased UV-B sensitivity of keratinocytes derived from KS patients. We show that the pro-inflammatory cytokines, IL-1ß, IL-6 and TNF-α, are upregulated in KS skin and in UV-B irradiated KS keratinocytes...
December 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27748861/biological-characterization-of-three-immortalized-esophageal-epithelial-cell-lines
#20
Fa-Min Zeng, Yang-Min Xie, Lian-Di Liao, Li-Yan Li, Bo Chen, Jian-Jun Xie, Li-Yan Xu, En-Min Li
The key molecular events that contribute to tumorigenesis are incompletely understood. The aim of the present study was to characterize and compare the biological phenotypes of three human telomerase reverse transcriptase (hTERT) and/or human papillomavirus 16 E6 and E7‑immortalized esophageal epithelial cell lines, NE2‑hTERT (NE2), NE3‑E6E7‑hTERT (NE3) and NEcA6‑E6E7‑hTERT (NEcA6). The present study used soft‑agar colony formation assays, tumorigenicity assays in nude mice, and cell proliferation, adhesion and migration assays to identify the biological characteristics of NE2, NE3 and NEcA6 cells...
November 2016: Molecular Medicine Reports
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