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Focal adhesion kinase

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https://www.readbyqxmd.com/read/28436949/p14arf-interacts-with-the-focal-adhesion-kinase-and-protects-cells-from-anoikis
#1
M Vivo, R Fontana, M Ranieri, G Capasso, T Angrisano, A Pollice, V Calabrò, G La Mantia
The ARF protein functions as an important sensor of hyper-proliferative stimuli restricting cell proliferation through both p53-dependent and -independent pathways. Although to date the majority of studies on ARF have focused on its anti-proliferative role, few studies have addressed whether ARF may also have pro-survival functions. Here we show for the first time that during the process of adhesion and spreading ARF re-localizes to sites of active actin polymerization and to focal adhesion points where it interacts with the phosphorylated focal adhesion kinase...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28432431/initial-cell-adhesion-of-three-cell-types-in-the-presence-and-absence-of-serum-proteins
#2
Martina Verdanova, Pavla Sauerova, Ute Hempel, Marie Hubalek Kalbacova
With the development of a wide range of new biomaterials for the sensing of different cell behaviour, it is important to consider whether the cells tested in vitro are in direct contact with the material or whether cell-biomaterial contact is mediated by an interfacial layer of proteins originating from the culture medium or from the cells themselves. Thus, this study describes the differences between the cell adhesion mediated by proteins originating from foetal bovine serum and without the presence of such proteins 2 h following cell seeding exemplarily with different cell types (an osteoblastic cell line, primary fibroblasts, and mesenchymal stem cells)...
April 21, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28427224/ponatinib-promotes-a-g1-cell-cycle-arrest-of-merlin-nf2-deficient-human-schwann-cells
#3
Alejandra M Petrilli, Jeanine Garcia, Marga Bott, Stephani Klingeman Plati, Christine T Dinh, Olena R Bracho, Denise Yan, Bing Zou, Rahul Mittal, Fred F Telischi, Xue-Zhong Liu, Long-Sheng Chang, D Bradley Welling, Alicja J Copik, Cristina Fernández-Valle
Neurofibromatosis type 2 (NF2) is a genetic syndrome that predisposes individuals to multiple benign tumors of the central and peripheral nervous systems, including vestibular schwannomas. Currently, there are no FDA approved drug therapies for NF2. Loss of function of merlin encoded by the NF2 tumor suppressor gene leads to activation of multiple mitogenic signaling cascades, including platelet-derived growth factor receptor (PDGFR) and SRC in Schwann cells. The goal of this study was to determine whether ponatinib, an FDA-approved ABL/SRC inhibitor, reduced proliferation and/or survival of merlin-deficient human Schwann cells (HSC)...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427180/mmp-11-promoted-the-oral-cancer-migration-and-fak-src-activation
#4
Chung-Han Hsin, Ying-Erh Chou, Shun-Fa Yang, Shih-Chi Su, Yi-Ting Chuang, Shu-Hui Lin, Chiao-Wen Lin
Matrix metalloproteinase-11 (MMP-11) has been observed in most invasive human carcinomas. The current study investigated the association between the clinicopathological characteristics and MMP-11 expression in oral squamous cell carcinoma (OSCC) patients. Immunohistochemistry (IHC) staining was performed to assess MMP-11 expression in 279 patients with OSCC. In addition, the metastatic effects of the MMP-11 overexpression on the OSCC cells were also investigated. We found that MMP-11 expression was present in 118/279 (42...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423494/control-of-long-distance-cell-to-cell-communication-and-autophagosome-transfer-in-squamous-cell-carcinoma-via-tunneling-nanotubes
#5
Inés Sáenz-de-Santa-María, Cristóbal Bernardo-Castiñeira, Eduardo Enciso, Inmaculada García-Moreno, Jose Luis Chiara, Carlos Suarez, María-Dolores Chiara
Tunneling nanotubes (TnTs) are thin channels that temporally connect nearby cells allowing the cell-to-cell trafficking of biomolecules and organelles. The presence or absence of TnTs in human neoplasms and the mechanisms of TnT assembly remains largely unexplored. In this study, we have identified TnTs in tumor cells derived from squamous cell carcinomas (SCC) cultured under bi-dimensional and tri-dimensional conditions and also in human SCC tissues. Our study demonstrates that TnTs are not specific of epithelial or mesenchymal phenotypes and allow the trafficking of endosomal/lysosomal vesicles, mitochondria, and autophagosomes between both types of cells...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421182/tgf-%C3%AE-1-pretreatment-improves-the-function-of-mesenchymal-stem-cells-in-the-wound-bed
#6
Deepraj Ghosh, Daniel J McGrail, Michelle R Dawson
The wound healing process initiates after injury to a tissue and involves a series of orchestrated events to minimize the invasion of foreign matters such as bacteria and efficiently regenerate the damaged tissue. A variety of cells must be recruited to the tissue during wound healing. However, this process is severely disrupted in patients suffering from chronic illness, including diabetes, leading to impaired healing or non-healing wounds. Current avenues of treatment include negative-pressure therapy, wound debridement, growth factor replacement, and cell-based therapies...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28418903/kinomic-profiling-identifies-focal-adhesion-kinase-1-as-a-therapeutic-target-in-advanced-clear-cell-renal-cell-carcinoma
#7
Arindam P Ghosh, Christopher D Willey, Joshua C Anderson, Karim Welaya, Dongquan Chen, Amitkumar Mehta, Pooja Ghatalia, Ankit Madan, Gurudatta Naik, Sunil Sudarshan, Guru Sonpavde
The introduction of targeted therapies has caused a paradigm shift in the treatment of metastatic clear cell (cc)-renal cell carcinoma (RCC). We hypothesized that determining differential kinase activity between primary and metastatic tumor sites may identify critical drivers of progression and relevant therapeutic targets in metastatic disease. Kinomic profiling was performed on primary tumor and metastatic tumor deposits utilizing a peptide substrate microarray to detect relative tyrosine phosphorylation activity...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417017/galectin-1-inhibition-attenuates-profibrotic-signaling-in-hypoxia-induced-pulmonary-fibrosis
#8
Jaymin J Kathiriya, Niyati Nakra, Jenna Nixon, Puja S Patel, Vijay Vaghasiya, Ahmed Alhassani, Zhi Tian, Diane Allen-Gipson, Vrushank Davé
Idiopathic pulmonary fibrosis (IPF) is characterized by lung remodeling arising from epithelial injury, aberrant fibroblast growth, and excessive deposition of extracellular matrix. Repeated epithelial injury elicits abnormal wound repair and lung remodeling, often associated with alveolar collapse and edema, leading to focal hypoxia. Here, we demonstrate that hypoxia is a physiological insult that contributes to pulmonary fibrosis (PF) and define its molecular roles in profibrotic activation of lung epithelial cells...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28416483/sfk-fak-signaling-attenuates-osimertinib-efficacy-in-both-drug-sensitive-and-drug-resistant-models-of-egfr-mutant-lung-cancer
#9
Eiki Ichihara, David Westover, Catherine B Meador, Yingjun Yan, Joshua A Bauer, Pengcheng Lu, Fei Ye, Amanda Kulick, Elisa De Stanchina, Robert McEwen, Marc Ladanyi, Darren Cross, William Pao, Christine M Lovly
Mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as osimertinib, are active agents for the treatment of EGFR-mutant lung cancer. Specifically, these agents can overcome the effects of the T790M mutation, which mediates resistance to first and second-generation EGFR TKI, and recent clinical trials have documented their efficacy in patients with EGFR-mutant lung cancer. Despite promising results, therapeutic efficacy is limited by development of acquired resistance...
April 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28416479/suppression-of-integrin-%C3%AE-3%C3%AE-1-by-%C3%AE-9%C3%AE-1-in-the-epidermis-controls-the-paracrine-resolution-of-wound-angiogenesis
#10
Whitney M Longmate, Scott P Lyons, Sridar V Chittur, Kevin M Pumiglia, Livingston Van De Water, C Michael DiPersio
Development of wound therapies is hindered by poor understanding of combinatorial integrin function in the epidermis. In this study, we generated mice with epidermis-specific deletion of α3β1, α9β1, or both integrins as well as keratinocyte lines expressing these integrin combinations. Consistent with proangiogenic roles for α3β1, α3-null keratinocytes showed reduced paracrine stimulation of endothelial cell migration and survival, and wounds of epidermis-specific α3 knockout mice displayed impaired angiogenesis...
April 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28415760/binding-of-galectin-1-to-integrin-%C3%AE-1-potentiates-drug-resistance-by-promoting-survivin-expression-in-breast-cancer-cells
#11
KeeSoo Nam, Seog-Ho Son, Sunhwa Oh, Donghwan Jeon, Hyungjoo Kim, Dong-Young Noh, Sangmin Kim, Incheol Shin
Galectin-1 is a β-galactoside binding protein secreted by many types of aggressive cancer cells. Although many studies have focused on the role of galectin-1 in cancer progression, relatively little attention has been paid to galectin-1 as an extracellular therapeutic target. To elucidate the molecular mechanisms underlying galectin-1-mediated cancer progression, we established galectin-1 knock-down cells via retroviral delivery of short hairpin RNA (shRNA) against galectin-1 in two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and Hs578T...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415713/mir-135a-inhibits-tumor-metastasis-and-angiogenesis-by-targeting-fak-pathway
#12
Zhenguo Cheng, Funan Liu, Hongyan Zhang, Xiaodong Li, Yanshu Li, Jiabin Li, Furong Liu, Yu Cao, Liu Cao, Feng Li
Tumor metastasis has been the major cause of recurrence and death in patients with gastric cancer. Here, we find miR-135a has a decreased expression in the metastatic cell lines compared with its parental cell lines by analyzing microRNA array. Further results show that miR-135a is downregulated in the majority of human gastric cancer tissues and cell lines. Decreased expression of miR-135a is associated with TNM stage and poor survival. Besides, regaining miR-135a in gastric cancer cells obviously inhibits tumor growth, migration, invasion and angiogenesis by targeting focal adhesion kinase (FAK) pathway...
March 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28406972/disruption-of-outer-blood-retinal-barrier-by-toxoplasma-gondii-infected-monocytes-is-mediated-by-paracrinely-activated-fak-signaling
#13
Hyun Beom Song, Hyoung-Oh Jun, Jin Hyoung Kim, Young-Ha Lee, Min-Ho Choi, Jeong Hun Kim
Ocular toxoplasmosis is mediated by monocytes infected with Toxoplasma gondii that are disseminated to target organs. Although infected monocytes can easily access to outer blood-retinal barrier due to leaky choroidal vasculatures, not much is known about the effect of T. gondii-infected monocytes on outer blood-retinal barrier. We prepared human monocytes, THP-1, infected with T. gondii and human retinal pigment epithelial cells, ARPE-19, grown on transwells as an in vitro model of outer blood-retinal barrier...
2017: PloS One
https://www.readbyqxmd.com/read/28406574/anti-tumor-effect-of-fak-inhibitor-pf562271-against-human-osteosarcoma-in-vitro-and-in-vivo
#14
Chuanzhen Hu, Xu Chen, Junxiang Wen, Liangzhi Gong, Zhuochao Liu, Jun Wang, Jing Liang, Fangqiong Hu, Qi Zhou, Li Wei, Yuhui Shen, Weibin Zhang
Focal adhesion kinase (FAK) overexpression is related to the invasive and metastatic property in different kind of cancers. Target therapy by inhibiting FAK has achieved promising effect in some cancer treatment, but its effect in human osteosarcoma has not yet well studied. In present study, we analyzed the anti-tumor efficacy of PF562271, a FAK inhibitor, against osteosarcoma in vitro and vivo. p-FAK (Y397) was highly expressed in primary human osteosarcoma tumor samples and was associated with osteosarcoma prognosis and lung metastasis...
April 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28406476/wisp-1-positively-regulates-angiogenesis-by-controlling-vegf-a-expression-in-human-osteosarcoma
#15
Hsiao-Chi Tsai, Huey-En Tzeng, Chun-Yin Huang, Yuan-Li Huang, Chun-Hao Tsai, Shih-Wei Wang, Po-Chuan Wang, An-Chen Chang, Yi-Chin Fong, Chih-Hsin Tang
In recent years, much research has focused on the role of angiogenesis in osteosarcoma, which occurs predominantly in adolescents and young adults. The vascular endothelial growth factor-A (VEGF-A) pathway is the key regulator of angiogenesis and in osteosarcoma. VEGF-A expression has been recognized as a prognostic marker in angiogenesis. Aberrant WNT1-inducible signaling pathway protein-1 (WISP-1) expression is associated with various cancers. However, the function of WISP-1 in osteosarcoma angiogenesis is poorly understood...
April 13, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28405684/sphk1-modulates-cell-migration-and-emt-related-marker-expression-by-regulating-the-expression-of-p-fak-in-colorectal-cancer-cells
#16
Chun-Yan Xu, Shi-Quan Liu, Meng-Bin Qin, Chun-Feng Zhuge, Lin Qin, Nan Qin, Ming-Yu Lai, Jie-An Huang
Sphingosine kinase 1 (SphK1) plays an important role in colorectal carcinoma metastasis. However, whether SphK1 modulates epithelial-mesenchymal transition (EMT)-related marker expression and the underlying mechanisms remain unclear. In this study, in order to clarify this issue, we used various colorectal cancer (CRC) cell lines, Caco2, HT29, RKO and HCT116. Each of the cell lines was divided into 3 groups as follows: the control group, SKI-Ⅱ (SphK1 inhibitor) group and PF-562271 [focal adhesion kinase (FAK) inhibitor] group...
May 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28398694/prognostic-significance-of-acp5-expression-in-patients-with-lung-adenocarcinoma
#17
Meirong Liu, Shuxiang Yang, Xiaofeng Tan
INTRODUCTION: Tartrate-resistant acid phosphatase 5 (ACP5), which is essential for bone resorption and osteoclast differentiation, promotes cell motility through the modulation of focal adhesion kinase phosphorylation. This study seeks to elucidate the association of ACP5 expression and the clinicopathologic characteristics of patients with lung adenocarcinoma Methods: The expression of ACP5 was measured by Immunohistochemistry and Western blot analysis in lung adenocarcinoma and matched tumor-adjacent tissues, and the χ2 test was applied to analyze the correlation between ACP5 expression and clinicopathologic features...
April 11, 2017: Clinical Respiratory Journal
https://www.readbyqxmd.com/read/28395993/salinomycin-attenuates-liver-cancer-stem-cell-motility-by-enhancing-cell-stiffness-and-increasing-f-actin-formation-via-the-fak-erk1-2-signalling-pathway
#18
Jinghui Sun, Qing Luo, Lingling Liu, Xianjiong Yang, Shunqin Zhu, Guanbin Song
Salinomycin has recently been identified as an antitumour drug for several types of cancer stem cell (CSC) treatments. However, the effects of salinomycin on the migratory and invasive properties of liver cancer stem cells (LCSCs) are unclear. In present study, we investigated the effect of salinomycin on the migration and invasion of LCSCs, and examined the molecular mechanisms underlying the anticancer effects of salinomycin. Here we showed that the migration and invasion of LCSCs were significantly suppressed in a salinomycin dose-dependent manner...
April 8, 2017: Toxicology
https://www.readbyqxmd.com/read/28395201/syndecan-4-deficiency-accelerates-the-transition-from-compensated-hypertrophy-to-heart-failure-following-pressure-overload
#19
Guannan Li, Jun Xie, Jianzhou Chen, Ran Li, Han Wu, Xinlin Zhang, Qinhua Chen, Rong Gu, Biao Xu
Increasing evidence suggests that a mismatch between angiogenesis and myocardial growth contributes to the transition from adaptive cardiac hypertrophy to heart failure following pressure overload. Syndecan-4 is a transmembrane proteoglycan that binds to growth factors and extracellular matrix proteins and is critical in focal adhesion formation. However, its effects on coronary angiogenesis during pressure overload-induced heart failure have not been studied. Here, we hypothesize that syndecan-4 modulates cardiac remodeling in response to pressure overload through its ability to regulate adaptive angiogenesis...
March 30, 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/28393238/modulation-of-interactions-of-neuroblastoma-cell-lines-with-extracellular-matrix-proteins-affects-their-sensitivity-to-treatment-with-the-anti-gd2-ganglioside-antibody-14g2a
#20
Irena Horwacik, Hanna Rokita
Children diagnosed with high risk neuroblastoma have poor prognosis which stimulates efforts to broaden therapies of the neoplasm. GD2-ganglioside (GD2) marks neuroblastoma cells and is a target for monoclonal antibodies. We have recently shown that some neuroblastoma cell lines are sensitive to direct cytotoxicity of the anti-GD2 mouse monoclonal antibody 14G2a (mAb). For IMR-32 and LA-N-1 cell lines, treatment with the 14G2a mAb induced evident changes in appearance such as cell rounding, aggregation, loose contact with culture plastic, or detachment...
April 7, 2017: International Journal of Oncology
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