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https://www.readbyqxmd.com/read/28218905/phosphorylation-mediated-activation-of-ldha-promotes-cancer-cell-invasion-and-tumour-metastasis
#1
L Jin, J Chun, C Pan, G N Alesi, D Li, K R Magliocca, Y Kang, Z G Chen, D M Shin, F R Khuri, J Fan, S Kang
Metastases remain the major cause of death from cancer. Recent molecular advances have highlighted the importance of metabolic alterations in cancer cells, including the Warburg effect that describes an increased glycolysis in cancer cells. However, how this altered metabolism contributes to tumour metastasis remains elusive. Here, we report that phosphorylation-induced activation of lactate dehydrogenase A (LDHA), an enzyme that catalyses the interconversion of pyruvate and lactate, promotes cancer cell invasion, anoikis resistance and tumour metastasis...
February 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28215542/hexachlorobenzene-alters-cell-cycle-by-regulating-p27-cyclin-e-cdk2-and-c-src-p27-protein-complexes
#2
C Ventura, M Núñez, V Gaido, C Pontillo, N Miret, A Randi, C Cocca
Hexachlorobenzene (HCB) is an organochlorine pollutant widely distributed in the environment around the entire world. Previous reports from our group and others have demonstrated that this compound is as an endocrine disruptor. We have also reported that HCB presents a co-carcinogenic effect in N-Nitroso-N-methyl-urea-induced mammary tumours in rats. In this work, we studied the effects of HCB on cell cycle progression and cell cycle regulating protein expression in the estrogen-sensitive breast cancer cell line, MCF-7...
February 12, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28208828/ginkgolic-acid-c-17-1-derived-from-ginkgo-biloba-leaves-suppresses-constitutive-and-inducible-stat3-activation-through-induction-of-pten-and-shp-1-tyrosine-phosphatase
#3
Seung Ho Baek, Jong Hyun Lee, Chulwon Kim, Jeong-Hyeon Ko, Seung-Hee Ryu, Seok-Geun Lee, Woong Mo Yang, Jae-Young Um, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Gautam Sethi, Kwang Seok Ahn
Ginkgolic acid C 17:1 (GAC 17:1) extracted from Ginkgo biloba leaves, has been previously reported to exhibit diverse antitumor effect(s) through modulation of several molecular targets in tumor cells, however the detailed mechanism(s) of its actions still remains to be elucidated. Signal transducer and activator of transcription 3 (STAT3) is an oncogenic transcription factor that regulates various critical functions involved in progression of diverse hematological malignancies, including multiple myeloma, therefore attenuating STAT3 activation may have a potential in cancer therapy...
February 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28192900/biphasic-affinity-chromatographic-approach-for-deep-tyrosine-phosphoproteome-analysis
#4
Zhenzhen Deng, Mingming Dong, Yan Wang, Jing Dong, Shawn S-C Li, Hanfa Zou, Mingliang Ye
Tyrosine phosphorylation (pTyr) is important for normal physiology and implicated in many human diseases, particularly cancer. Identification of pTyr sites is critical to dissecting signaling pathways and understanding disease pathologies. However, compared with serine/threonine phosphorylation (pSer/pThr), the analysis of pTyr at the proteome level is more challenging due to its low abundance. Here, we developed a biphasic affinity chromatographic approach where Src SH2 superbinder was coupled with NeutrAvidin affinity chromatography, for tyrosine phosphoproteome analysis...
February 1, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28184941/combined-effects-of-furanodiene-and-doxorubicin-on-the-migration-and-invasion-of-mda-mb-231-breast-cancer-cells-in-vitro
#5
Zhang-Feng Zhong, Wen Tan, Ke Tian, Hua Yu, Wen-An Qiang, Yi-Tao Wang
Furanodiene is one of the major bioactive components isolated from the natural product of the plant, Curcuma wenyujin Y.H. Chen et C. Ling. Furanodiene has been found to exert anticancer effects in various types of cancer cell lines, as well as exhibit antimetastatic activities. However, the antimetastatic capacity of furanodiene in combination with the common chemotherapy drug doxorubicin has not been investigated. We found that doxorubicin at a non-toxic concentration induced cell migration and cell invasion in highly metastatic breast cancer cells...
February 10, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28123075/ron-kinase-a-target-for-treatment-of-cancer-induced-bone-destruction-and-osteoporosis
#6
Kelsi Andrade, Jaime Fornetti, Ling Zhao, Scott C Miller, R Lor Randall, Neysi Anderson, Susan E Waltz, Mark McHale, Alana L Welm
Bone destruction occurs in aging and numerous diseases, including osteoporosis and cancer. Many cancer patients have bone osteolysis that is refractory to state-of-the-art treatments, which block osteoclast activity with bisphosphonates or by inhibiting the receptor activator of nuclear factor κB ligand (RANKL) pathway. We previously showed that macrophage-stimulating protein (MSP) signaling, which is elevated in about 40% of breast cancers, promotes osteolytic bone metastasis by activation of the MSP signaling pathway in tumor cells or in the bone microenvironment...
January 25, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28076322/aeroallergen-der-p-2-promotes-motility-of-human-non-small-cell-lung-cancer-cells-via-toll-like-receptor-mediated-up-regulation-of-urokinase-type-plasminogen-activator-and-integrin-focal-adhesion-kinase-signaling
#7
Chun-Hsiang Lin, Hui-Han Lin, Cheng-Yi Kuo, Shao-Hsuan Kao
House dust mite (HDM) allergens are one of the major causes leading to respiratory hypersensitiveness and airway remodeling. Here we hypothesized that a major HDM allergen Der p 2 could increase cell motility and invasiveness of non-small cell lung cancer (NSCLC) cells. Our results showed that low dose (1 and 3 μg/mL) recombinant Der p 2 protein (DP2) enhanced the migration and invasiveness of human NSCLC cell A549, H1299 and CL1-5, but nonsignificantly altered their growth. Further investigation revealed that integrin αV level was increased and its downstream signaling including focal adhesion kinase (FAK) and paxillin were activated in A549 cells exposed to DP2...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28069687/adaptive-resistance-of-melanoma-cells-to-raf-inhibition-via-reversible-induction-of-a-slowly-dividing-de-differentiated-state
#8
Mohammad Fallahi-Sichani, Verena Becker, Benjamin Izar, Gregory J Baker, Jia-Ren Lin, Sarah A Boswell, Parin Shah, Asaf Rotem, Levi A Garraway, Peter K Sorger
Treatment of BRAF-mutant melanomas with MAP kinase pathway inhibitors is paradigmatic of the promise of precision cancer therapy but also highlights problems with drug resistance that limit patient benefit. We use live-cell imaging, single-cell analysis, and molecular profiling to show that exposure of tumor cells to RAF/MEK inhibitors elicits a heterogeneous response in which some cells die, some arrest, and the remainder adapt to drug. Drug-adapted cells up-regulate markers of the neural crest (e.g., NGFR), a melanocyte precursor, and grow slowly...
January 9, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28036267/microrna-603-acts-as-a-tumor-suppressor-and-inhibits-triple-negative-breast-cancer-tumorigenesis-by-targeting-elongation-factor-2-kinase
#9
Recep Bayraktar, Martin Pichler, Pinar Kanlikilicer, Cristina Ivan, Emine Bayraktar, Nermin Kahraman, Burcu Aslan, Serpil Oguztuzun, Mustafa Ulasli, Ahmet Arslan, George Calin, Gabriel Lopez-Berestein, Bulent Ozpolat
Triple negative breast cancer (TNBC) is an aggressive type of breast cancer characterized by the absence of defined molecular targets, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and is associated with high rates of relapse and distant metastasis despite surgery and adjuvant chemotherapy. The lack of effective targeted therapies for TNBC represents an unmet therapeutic challenge. Eukaryotic elongation factor 2 kinase (eEF2K) is an atypical calcium/calmodulin-dependent serine/threonine kinase that promotes TNBC tumorigenesis, progression, and drug resistance, representing a potential novel molecular target...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28011194/convergence-of-eicosanoid-and-integrin-biology-role-of-src-in-12-lox-activation
#10
Ashok-Kumar Dilly, Keqin Tang, Yande Guo, Sangeeta Joshi, Prasanna Ekambaram, Krishna Rao Maddipati, Yinlong Cai, Stephanie C Tucker, Kenneth V Honn
12-Lipoxygenase (12-LOX) metabolizes arachidonic acid to 12(S)-hydroxyeicosatetraenoic acid, or 12(S)-HETE, a proinflammatory bioactive lipid implicated in tumor angiogenesis, growth, and metastasis. The mechanisms underlying 12-LOX-mediated signaling in cancer progression are still ill-defined. In the present study we demonstrate that 12-LOX phosphorylation and subsequent enzymatic activity occurs after integrin β4 stimulation and Src kinase recruitment to the integrin subunit. Inhibition of Src activity by PP2 or Src dominant-negative mutants reduced 12-LOX tyrosine phosphorylation and 12(S)-HETE production in response to integrin β4 stimulation in A431 cells...
February 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28008134/interacting-post-muscarinic-receptor-signaling-pathways-potentiate-matrix-metalloproteinase-1-expression-and-invasion-of-human-colon-cancer-cells
#11
Anan Said, Shien Hu, Ameer Abutaleb, Tonya Watkins, Kunrong Cheng, Ahmed Chahdi, Panjamurthy Kuppusamy, Neeraj Saxena, Guofeng Xie, Jean-Pierre Raufman
M3 muscarinic receptor (M3R) expression is increased in colon cancer; M3R activation stimulates colon cancer cell invasion via cross-talk with epidermal growth factor receptors (EGFR), post-EGFR activation of mitogen-activated protein kinase (MAPK) ERK1/2, and induction of matrix metalloproteinase-1 ( MMP1 ) expression. MMP1 expression is strongly associated with tumor metastasis and adverse outcomes. Here, we asked whether other MAPKs regulate M3R agonist-induced MMP1 expression. In addition to activating ERK1/2, we found that treating colon cancer cells with acetylcholine (ACh) stimulated robust time- and dose-dependent phosphorylation of p38 MAPK...
December 22, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27998964/phase-2-placebo-controlled-double-blind-trial-of-dasatinib-added-to-gemcitabine-for-patients-with-locally-advanced-pancreatic-cancer
#12
T R J Evans, E Van Cutsem, M J Moore, I S Bazin, A Rosemurgy, G Bodoky, G Deplanque, M Harrison, B Melichar, D Pezet, A Elekes, E Rock, C Lin, L Strauss, P J O'Dwyer
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate with limited treatment options. Gemcitabine provides a marginal survival benefit for patients with advanced PDAC. Dasatinib is a competitive inhibitor of Src kinase, which is overexpressed in PDAC tumors. Dasatinib and gemcitabine were combined in a phase 1 clinical trial where stable disease was achieved in 2 of 8 patients with gemcitabine-refractory PDAC. PATIENTS AND METHODS: This placebo-controlled, randomized, double-blind, phase II study compared the combination of gemcitabine plus dasatinib to gemcitabine plus placebo in patients with locally advanced, non-metastatic PDAC...
December 19, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27995987/intrinsic-photosensitivity-enhances-motility-of-t-lymphocytes
#13
Thieu X Phan, Barbara Jaruga, Sandeep C Pingle, Bidhan C Bandyopadhyay, Gerard P Ahern
Sunlight has important biological effects in human skin. Ultraviolet (UV) light striking the epidermis catalyzes the synthesis of Vitamin D and triggers melanin production. Although a causative element in skin cancers, sunlight is also associated with positive health outcomes including reduced incidences of autoimmune diseases and cancers. The mechanisms, however, by which light affects immune function remain unclear. Here we describe direct photon sensing in human and mouse T lymphocytes, a cell-type highly abundant in skin...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27980342/evaluation-of-a-tyrosine-kinase-peptide-microarray-for-tyrosine-kinase-inhibitor-therapy-selection-in-cancer
#14
Mariette Labots, Kristy J Gotink, Henk Dekker, Kaamar Azijli, Johannes C van der Mijn, Charlotte M Huijts, Sander R Piersma, Connie R Jiménez, Henk M W Verheul
Personalized cancer medicine aims to accurately predict the response of individual patients to targeted therapies, including tyrosine kinase inhibitors (TKIs). Clinical implementation of this concept requires a robust selection tool. Here, using both cancer cell lines and tumor tissue from patients, we evaluated a high-throughput tyrosine kinase peptide substrate array to determine its readiness as a selection tool for TKI therapy. We found linearly increasing phosphorylation signal intensities of peptides representing kinase activity along the kinetic curve of the assay with 7...
December 16, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27931239/mcl-1-inhibition-provides-a-new-way-to-suppress-breast-cancer-metastasis-and-increase-sensitivity-to-dasatinib
#15
Adelaide I J Young, Andrew M K Law, Lesley Castillo, Sabrina Chong, Hayley D Cullen, Martin Koehler, Sebastian Herzog, Tilman Brummer, Erinna F Lee, Walter D Fairlie, Morghan C Lucas, David Herrmann, Amr Allam, Paul Timpson, D Neil Watkins, Ewan K A Millar, Sandra A O'Toole, David Gallego-Ortega, Christopher J Ormandy, Samantha R Oakes
BACKGROUND: Metastatic disease is largely resistant to therapy and accounts for almost all cancer deaths. Myeloid cell leukemia-1 (MCL-1) is an important regulator of cell survival and chemo-resistance in a wide range of malignancies, and thus its inhibition may prove to be therapeutically useful. METHODS: To examine whether targeting MCL-1 may provide an effective treatment for breast cancer, we constructed inducible models of BIMs2A expression (a specific MCL-1 inhibitor) in MDA-MB-468 (MDA-MB-468-2A) and MDA-MB-231 (MDA-MB-231-2A) cells...
December 8, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27922739/tyrosine-kinase-aurora-kinase-and-leucine-aminopeptidase-as-attractive-drug-targets-in-anticancer-therapy-characterisation-of-their-inhibitors
#16
Joanna Ziemska, Jolanta Solecka
Cancers are the leading cause of deaths all over the world. Available anticancer agents used in clinics exhibit low therapeutic index and usually high toxicity. Wide spreading drug resistance of cancer cells induce a demanding need to search for new drug targets. Currently, many on-going studies on novel compounds with potent anticancer activity, high selectivity as well as new modes of action are conducted. In this work, we describe in details three enzyme groups, which are at present of extensive interest to medical researchers and pharmaceutical companies...
2016: Roczniki Państwowego Zakładu Higieny
https://www.readbyqxmd.com/read/27847941/atomic-force-microscopy-and-graph-analysis-to-study-the-p-cadherin-sfk-mechanotransduction-signalling-in-breast-cancer-cells
#17
A S Ribeiro, F A Carvalho, J Figueiredo, R Carvalho, T Mestre, J Monteiro, A F Guedes, M Fonseca, J Sanches, R Seruca, N C Santos, J Paredes
Physical forces mediated by cell-cell adhesion molecules, as cadherins, play a crucial role in preserving normal tissue architecture. Accordingly, altered cadherins' expression has been documented as a common event during cancer progression. However, in most studies, no data exist linking pro-tumorigenic signaling and variations in the mechanical balance mediated by adhesive forces. In breast cancer, P-cadherin overexpression increases in vivo tumorigenic ability, as well as in vitro cell invasion, by activating Src family kinase (SFK) signalling...
November 16, 2016: Nanoscale
https://www.readbyqxmd.com/read/27809841/pharmacological-targeting-of-cxcl12-cxcr4-signaling-in-prostate-cancer-bone-metastasis
#18
M Katie Conley-LaComb, Louie Semaan, Rajareddy Singareddy, Yanfeng Li, Elisabeth I Heath, Seongho Kim, Michael L Cher, Sreenivasa R Chinni
BACKGROUND: The CXCL12/CXCR4 axis transactivates HER2 and promotes intraosseous tumor growth. To further explore the transactivation of HER2 by CXCL12, we investigated the role of small GTP protein Gαi2 in Src and HER2 phosphorylation in lipid raft membrane microdomains and the significance of CXCR4 in prostate cancer bone tumor growth. METHODS: We used a variety of methods such as lipid raft isolation, invasion assays, an in vivo model of intratibial tumor growth, bone histomorphometry, and immunohistochemistry to determine the role of CXCR4 signaling in lipid raft membrane microdomains and effects of targeting of CXCR4 for bone tumor growth...
November 3, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27787230/integrated-in-silico-in-vitro-characterization-identification-and-disruption-of-the-intermolecular-interaction-between-sh3-domain-containing-protein-kinases-and-human-pituitary-tumor-transforming-gene-1
#19
Yanan Li, Mengmeng Li, Weijie Min, Guosheng Han, Laixing Wang, Chao Chen, Zifu Li, Yuhui Zhang, Jianmin Li, Zhijian Yue
The human pituitary tumor-transforming gene-1 (hPTTG1) has been found to be overexpressed in various cancers. Accumulated evidences implicate that some of protein kinases can specifically recognize two PXXP motifs at hPTTG1 C-terminus through their Src homology (SH3) domain and then phosphorylate the protein by their catalytic domain. Here, we integrate in silico analysis and in vitro assay to characterize the intermolecular interaction between the two hPTTG1 motif peptides 161LGPPSPVK168 (M1P) and 168KMPSPPWE175 (M2P) and the SH3 domains of Ser/Thr-specific protein kinases MAP3K and PI3K...
January 2017: General Physiology and Biophysics
https://www.readbyqxmd.com/read/27766744/pttg1-levels-are-predictive-of-saracatinib-sensitivity-in-ovarian-cancer-cell-lines
#20
I Nakachi, B A Helfrich, M A Spillman, E A Mickler, C J Olson, J L Rice, C D Coldren, L E Heasley, M W Geraci, R S Stearman
Src kinase is recognized as a key target for molecular cancer therapy. However, methods to efficiently select patients responsive to Src inhibitors are lacking. We explored the sensitivity of ovarian cancer cell lines to the Src kinase inhibitor saracatinib to identify predictive markers of drug sensitivity using gene microarrays. Pituitary tumor transforming gene 1 (PTTG1) was selected as a potential biomarker as mRNA levels were correlated with saracatinib resistance, as well as higher PTTG1 protein expression...
December 2016: Clinical and Translational Science
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