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Integrin linked kinase

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https://www.readbyqxmd.com/read/28188308/tetraspanin-8-is-a-novel-regulator-of-ilk-driven-%C3%AE-1-integrin-adhesion-and-signaling-in-invasive-melanoma-cells
#1
Manale El Kharbili, Clément Robert, Tiffany Witkowski, Emmanuelle Danty-Berger, Laetitia Barbollat-Boutrand, Ingrid Masse, Nicolas Gadot, Arnaud de la Fouchardière, Paul C McDonald, Shoukat Dedhar, François Le Naour, Françoise Degoul, Odile Berthier-Vergnes
Melanoma is well known for its propensity for lethal metastasis and resistance to most current therapies. Tumor progression and drug resistance depend to a large extent on the interplay between tumor cells and the surrounding matrix. We previously identified Tetraspanin 8 (Tspan8) as a critical mediator of melanoma invasion, whose expression is absent in healthy skin. The present study investigated whether Tspan8 may influence cell-matrix anchorage and regulate downstream molecular pathways leading to an aggressive behavior...
February 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28188026/clinical-significance-of-integrin-linked-kinase-in-laryngeal-squamous-cell-carcinoma
#2
Ping-An Wu, Shi-Sheng Li, Qing-Lai Tang, Bing-Bing Liu, Xin-Ming Yang
OBJECTIVE: To investigate the expression of integrin-linked kinase (ILK) and its relationship with clinicopathological parameters in laryngeal squamous cell carcinoma (LSCC). METHODS: 116 patients who had previously undergone complete resection of tumor for LSCC were studied retrospectively. The level of ILK expression in tumor tissues and adjacent nontumor tissues were determined by immunohistochemistry. RESULTS: Increased expression of ILK was found in 65...
February 7, 2017: Auris, Nasus, Larynx
https://www.readbyqxmd.com/read/28167044/hypoxia-directs-human-extravillous-trophoblast-differentiation-in-a-hypoxia-inducible-factor-dependent-manner
#3
Anna K Wakeland, Francesca Soncin, Matteo Moretto-Zita, Ching-Wen Chang, Mariko Horii, Don Pizzo, Katharine K Nelson, Louise C Laurent, Mana M Parast
Villous cytotrophoblasts are epithelial stem cells of the early human placenta, able to differentiate either into syncytiotrophoblasts in floating chorionic villi or extravillous trophoblasts (EVTs) at the anchoring villi. The signaling pathways regulating differentiation into these two lineages are incompletely understood. The bulk of placental growth and development in the first trimester occurs under low oxygen tension. One major mechanism by which oxygen regulates cellular function is through the hypoxia-inducible factor (HIF), a transcription factor complex stabilized under low oxygen tension to mediate cellular responses, including cell fate decisions...
February 3, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28159878/laminins-in-epithelial-cell-polarization-old-questions-in-search-of-new-answers
#4
Karl S Matlin, Satu-Marja Myllymäki, Aki Manninen
Laminin, a basement membrane protein discovered in 1979, was shortly thereafter implicated in the polarization of epithelial cells in both mammals and a variety of lower organisms. To transduce a spatial cue to the intrinsic polarization machinery, laminin must polymerize into a dense network that forms the foundation of the basement membrane. Evidence suggests that activation of the small GTPase Rac1 by β1-integrins mobilizes laminin-binding integrins and dystroglycan to consolidate formation of the laminin network and initiate rearrangements of both the actin and microtubule cytoskeleton to help establish the apicobasal axis...
February 3, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28138714/overexpression-of-ilk-promotes-temozolomide-resistance-in-glioma-cells
#5
Feng Liang, Bing Wang, Long Bao, Yin-Sheng Zhao, Shi-Min Zhang, Shu-Qin Zhang
The present study aimed to investigate whether overexpression of integrin-linked kinase (ILK) affects drug resistance to temozolomide (TMZ) in glioma cells. To do this, a plasmid containing the ILK gene was transfected into the SHG‑44 human glioma cell line, and cells were subsequently cultured in the absence or presence of TMZ. The expression levels of ILK, multidrug resistance‑associated protein (MRP) and multi‑drug resistance protein (MDR) were assessed in these cells. Cell growth and apoptosis were measured by MTT and Hoechst staining, and flow cytometry, respectively...
March 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28134933/inhibition-of-the-integrin-fak-signaling-axis-and-c-myc-synergistically-disrupts-ovarian-cancer-malignancy
#6
B Xu, J Lefringhouse, Z Liu, D West, L A Baldwin, C Ou, L Chen, D Napier, L Chaiswing, L D Brewer, D St Clair, O Thibault, J R van Nagell, B P Zhou, R Drapkin, J-A Huang, M L Lu, F R Ueland, X H Yang
Integrins, a family of heterodimeric receptors for extracellular matrix, are promising therapeutic targets for ovarian cancer, particularly high-grade serous-type (HGSOC), as they drive tumor cell attachment, migration, proliferation and survival by activating focal adhesion kinase (FAK)-dependent signaling. Owing to the potential off-target effects of FAK inhibitors, disruption of the integrin signaling axis remains to be a challenge. Here, we tackled this barrier by screening for inhibitors being functionally cooperative with small-molecule VS-6063, a phase II FAK inhibitor...
January 30, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28109308/semaphorin-7a-as-a-potential-immune-regulator-and-promising-therapeutic-target-in-rheumatoid-arthritis
#7
Jianmin Xie, Hao Wang
BACKGROUND: Semaphorin 7A (Sema7A) is expressed by several different classes of lymphoid and myeloid cells and is a potent immunomodulator. We examined the role of Sema7A in modulating cellular immune responses and to provide experimental data validating the therapeutic potential of Sema7A in rheumatoid arthritis (RA). METHODS: Soluble Sema7A (sSema7A) levels in the serum and synovial fluid from patients with RA or osteoarthritis, as well as cytokine secretions, were analyzed with an enzyme-linked immunosorbent assay...
January 21, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28108607/insulin-like-growth-factor-binding-protein-1-could-improve-glucose-regulation-and-insulin-sensitivity-through-its-rgd-domain
#8
Natalie J Haywood, Paul A Cordell, Kar Yeun Tang, Natallia Makova, Nadira Y Yuldasheva, Helen Imrie, Hema Viswambharan, Alexander F Bruns, Richard M Cubbon, Mark T Kearney, Stephen B Wheatcroft
Low circulating levels of insulin-like growth factor binding protein 1 (IGFBP-1) are associated with insulin resistance and predict the development of type 2 diabetes. IGFBP-1 can affect cellular functions independently of IGF binding through an Arg-Gly-Asp (RGD) integrin-binding motif. Whether causal mechanisms underlie the favorable association of high IGFBP-1 levels with insulin sensitivity and whether these could be exploited therapeutically remain unexplored. We used recombinant IGFBP-1 and a synthetic RGD-containing hexapeptide in complementary in vitro signaling assays and in vivo metabolic profiling in obese mice to investigate the effects of IGFBP-1 and its RGD domain on insulin sensitivity, insulin secretion, and whole-body glucose regulation...
February 2017: Diabetes
https://www.readbyqxmd.com/read/28106780/integrins-and-cell-metabolism-an-intimate-relationship-impacting-cancer
#9
REVIEW
Rehman Ata, Costin N Antonescu
Integrins are important regulators of cell survival, proliferation, adhesion and migration. Once activated, integrins establish a regulated link between the extracellular matrix and the cytoskeleton. Integrins have well-established functions in cancer, such as in controlling cell survival by engagement of many specific intracellular signaling pathways and in facilitating metastasis. Integrins and associated proteins are regulated by control of transcription, membrane traffic, and degradation, as well as by a number of post-translational modifications including glycosylation, allowing integrin function to be modulated to conform to various cellular needs and environmental conditions...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28077718/integrin-linked-kinase-ilk-deletion-disrupts-oligodendrocyte-development-by-altering-cell-cycle
#10
Rashad Hussain, Wendy B Macklin
: During development, oligodendrocytes are initially specified, after which oligodendrocyte precursor cells (OPCs) migrate and proliferate before differentiating into myelinating cells. Lineage-specific programming of oligodendrocytes results from sensing environmental cues through membrane-bound receptors and related intracellular signaling molecules. Integrin-linked kinase (ILK) is an important protein that is expressed at the inner margins of the plasma membrane and can mediate some of these signals...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28069177/increased-expression-of-integrin-linked-kinase-during-decidualization-regulates-the-morphological-transformation-of-endometrial-stromal-cells
#11
Chih-Feng Yen, Sung Hoon Kim, Shuen-Kuei Liao, Cem Atabekoglu, Serpil Uckac, Aydin Arici, Sefa Arlier, Chyi-Long Lee, Hsin-Shih Wang, Umit A Kayisli
OBJECTIVE: To study the impact of integrin-linked kinase (ILK) in endometrial stromal cells (ESCs) during decidualization. DESIGN: Laboratory study with the use of human endometrium. SETTING: University hospital. PATIENT(S): Fertile reproductive-age women who had not received hormonal treatment for 3 months before tissue collection. INTERVENTION(S): Endometrium tissue collection, in vitro decidualization of isolated ESCs, and small interfering (si) RNA transfection...
January 6, 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28061467/cytological-study-on-the-regulation-of-lymphocyte-homing-in-the-chicken-spleen-during-lps-stimulation
#12
Qian Zhang, Yasir Waqas, Ping Yang, Xuejing Sun, Yi Liu, Nisar Ahmed, Bing Chen, Quanfu Li, Lisi Hu, Yufei Huang, Hong Chen, Bing Hu, Qiusheng Chen
The immune function of the chicken spleen depends on its different compartments of red and white pulps, but little is known about the mechanism underlying lymphocyte homing towards the different compartments. In the present study, the role of lymphocyte homing in the chicken spleen was investigated during lipopolysaccharide (LPS) stimulation. Morphological analysis demonstrated the cuboidal endothelial cells of the splenic sheathed capillary facilitated the passage of lymphocyte homing to the chicken spleen...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28050799/thyroid-hormone-controls-breast-cancer-cell-movement-via-integrin-%C3%AE-v-%C3%AE-3-src-fak-pi3-kinases
#13
Marina Inés Flamini, Ivonne Denise Uzair, Gisela Erika Pennacchio, Flavia Judith Neira, Joselina Magali Mondaca, Fernando Dario Cuello-Carrión, Graciela Alma Jahn, Tommaso Simoncini, Angel Matías Sanchez
Thyroid hormones (TH) play a fundamental role in diverse processes, including cellular movement. Cell migration requires the integration of events that induce changes in cell structure towards the direction of migration. These actions are driven by actin remodeling and stabilized by the development of adhesion sites to extracellular matrix via transmembrane receptors linked to the actin cytoskeleton. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that promotes cell migration and invasion through the control of focal adhesion turnover...
January 3, 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28045035/pdlim5-links-kidney-anion-exchanger-1-kae1-to-ilk-and-is-required-for-membrane-targeting-of-kae1
#14
Ya Su, Thomas F Hiemstra, Yahui Yan, Juan Li, Hannah I Karet, Lawrence Rosen, Pablo Moreno, Fiona E Karet Frankl
Anion exchanger 1 (AE1) mediates Cl(-)/HCO3(-) exchange in erythrocytes and kidney intercalated cells where it functions to maintain normal bodily acid-base homeostasis. AE1's C-terminal tail (AE1C) contains multiple potential membrane targeting/retention determinants, including a predicted PDZ binding motif, which are critical for its normal membrane residency. Here we identify PDLIM5 as a direct binding partner for AE1 in human kidney, via PDLIM5's PDZ domain and the PDZ binding motif in AE1C. Kidney AE1 (kAE1), PDLIM5 and integrin-linked kinase (ILK) form a multiprotein complex in which PDLIM5 provides a bridge between ILK and AE1C...
January 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28031460/the-inhibitory-role-of-%C3%AE-2-6-sialylation-in-adipogenesis
#15
Tomoko Kaburagi, Yasuhiko Kizuka, Shinobu Kitazume, Naoyuki Taniguchi
Adipose tissue plays critical roles in obesity and related diseases such as diabetes and cardiovascular diseases. Previous reports suggest that glycans, the most common posttranslational modifications, are involved in obesity-related diseases, but what type of glycan regulates adipogenesis during obesity remains unclear. In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28011283/integrin-linked-kinase-regulates-cellular-mechanics-facilitating-the-motility-in-3d-extracellular-matrices
#16
Tom Kunschmann, Stefanie Puder, Tony Fischer, Jeremy Perez, Nils Wilharm, Claudia Tanja Mierke
The motility of cells plays an important role for many processes such as wound healing and malignant progression of cancer. The efficiency of cell motility is affected by the microenvironment. The connection between the cell and its microenvironment is facilitated by cell-matrix adhesion receptors and upon their activation focal adhesion proteins such as integrin-linked kinase (ILK) are recruited to sites of focal adhesion formation. In particular, ILK connects cell-matrix receptors to the actomyosin cytoskeleton...
December 21, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27995929/the-biomechanical-properties-of-an-epithelial-tissue-determine-the-location-of-its-vasculature
#17
Martin Kragl, Rajib Schubert, Haiko Karsjens, Silke Otter, Barbara Bartosinska, Kay Jeruschke, Jürgen Weiss, Chunguang Chen, David Alsteens, Oliver Kuss, Stephan Speier, Daniel Eberhard, Daniel J Müller, Eckhard Lammert
An important question is how growing tissues establish a blood vessel network. Here we study vascular network formation in pancreatic islets, endocrine tissues derived from pancreatic epithelium. We find that depletion of integrin-linked kinase (ILK) in the pancreatic epithelial cells of mice results in glucose intolerance due to a loss of the intra-islet vasculature. In turn, blood vessels accumulate at the islet periphery. Neither alterations in endothelial cell proliferation, apoptosis, morphology, Vegfa expression and VEGF-A secretion nor 'empty sleeves' of vascular basement membrane are found...
December 20, 2016: Nature Communications
https://www.readbyqxmd.com/read/27986909/sos1-arhgef1-and-dock2-rho-gefs-mediate-jak-dependent-lfa-1-activation-by-chemokines
#18
Lara Toffali, Alessio Montresor, Michela Mirenda, Giorgio Scita, Carlo Laudanna
JAK-dependent activation of the rho module of integrin affinity triggering mediates chemokine-induced leukocyte adhesion. However, the signaling events linking JAKs to rho small GTPase activation by chemokines is still incompletely described. In this study, we show that son of sevenless 1 (SOS1), rho guanine nucleotide exchange factor (GEF)1 (ARHGEF1), and dedicator of cytokinesis (DOCK)2 GEFs mediate CXCL12-induced LFA-1 activation in human primary T lymphocytes. Downregulated expression of SOS1, ARHGEF1, and DOCK2 impairs LFA-1-mediated rapid T lymphocyte adhesion as well as underflow arrest on ICAM-1 induced by CXCL12...
December 16, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27982018/sio2-antisense-molecules-covered-by-nepetalactone-extracted-from-nepeta-gloeocephala-inhibits-ilk-phosphorylation-and-downstream-pkb-akt-signaling-in-hela-cells
#19
M Dehghany Ashkezary, F Aboee-Mehrizi, P Moradi
In this study, the anticancer property of SiO2@antisense molecules (SiO2@AMs) and SiO2@AM covered by nepetalactone (SiO2@AM/CN), extracted from Nepeta gloeocephala, was investigated. Here integrin-linked kinase (ILK) phosphorylation and protein kinase B/AKT (PKB/AKT) signaling was studied when HeLa cells were exposed to SiO2@AM and SiO2@AM/CN. First, N. gloeocephala was identified at the Iranian National Herbarium. Then, its essential oil (EO) was obtained by the hydrodistillation method. In the next step, 4aα,7α,7aα-nepetalactone was extracted from the EO, based on the spectroscopic data...
December 16, 2016: Cancer Gene Therapy
https://www.readbyqxmd.com/read/27936345/targeting-integrin-linked-kinase-to-suppress-oncogenic-kras-signaling-in-pancreatic-cancer
#20
Po-Chen Chu, Samuel K Kulp, Tanios Bekaii-Saab, Ching-Shih Chen
Although oncogenic KRAS represents a therapeutically relevant target in pancreatic cancer, it is deemed "non-druggable" because of the intrinsic difficulty in designing direct inhibitors of KRAS. Our recent work demonstrated a KRAS-integrin-linked kinase (ILK) regulatory feedback loop that allows pancreatic cancer cells to regulate KRAS expression and to interact with the tumor microenvironment to promote aggressive phenotype. KRAS induces E2F1-mediated transcriptional activation of ILK expression, and ILK, in turn, controls KRAS expression via hnRNPA1, which binds and destabilizes the G-quadruplex in the KRAS promoter...
December 9, 2016: Small GTPases
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