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c Src kinase and cancer

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https://www.readbyqxmd.com/read/29340103/anti-neoplastic-drugs-increase-caveolin-1-dependent-migration-invasion-and-metastasis-of-cancer-cells
#1
Natalia I Díaz-Valdivia, Claudia C Calderón, Jorge E Díaz, Lorena Lobos-González, Hugo Sepulveda, Rina J Ortíz, Samuel Martinez, Veronica Silva, Horacio J Maldonado, Patricio Silva, Sergio Wehinger, Verónica A Burzio, Vicente A Torres, Martín Montecino, Lisette Leyton, Andrew F G Quest
Expression of the scaffolding protein Caveolin-1 (CAV1) enhances migration and invasion of metastatic cancer cells. Yet, CAV1 also functions as a tumor suppressor in early stages of cancer, where expression is suppressed by epigenetic mechanisms. Thus, we sought to identify stimuli/mechanisms that revert epigenetic CAV1 silencing in cancer cells and evaluate how this affects their metastatic potential. We reasoned that restricted tissue availability of anti-neoplastic drugs during chemotherapy might expose cancer cells to sub-therapeutic concentrations, which activate signaling pathways and the expression of CAV1 to favor the acquisition of more aggressive traits...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29324735/influence-of-c-src-on-hypoxic-resistance-to-paclitaxel-in-human-ovarian-cancer-cells-and-reversal-of-fv-429
#2
Qinglong Guo, Lu Lu, Yan Liao, Xiaoping Wang, Yi Zhang, Yicheng Liu, Shaoliang Huang, Haopeng Sun, Zhiyu Li, Li Zhao
SRC family kinase was documented to have vital roles in adjusting cancer cell malignant behaviors. To date, the role of c-Src, a member of SRC family kinase, in resistance to paclitaxel in human ovarian cancer cells under hypoxia has not been investigated. In the present study, we discovered that hypoxic environment suppressed paclitaxel-induced G2/M phase arrest and blockade of c-Src improved ovarian cancer cells' sensitivity to paclitaxel. FV-429, a derivative of natural flavonoid wogonin, could suppress gene expression and activation of c-Src, followed by deteriorated Stat3 nuclear translocation and its binding to HIF-1α, resulting in paclitaxel resistance reversal through G2/M arrest potentiation...
January 11, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29312563/trkb-promotes-laryngeal-cancer-metastasis-via-activation-pi3k-akt-pathway
#3
Liang Jiang, Zhihai Wang, Chuan Liu, Zhitao Gong, Yucheng Yang, Houyong Kang, Yanshi Li, Guohua Hu
Objectives: The aim of our study was to investigate the role of TrkB pathway in tumor occurrence and development for in order to provide theoretical basis to laryngeal cancer therapy. Materials and methods: Biological characteristics of the cells were studied by migration tests and colony forming assay. Gene and protein expression analysis was performed by RT-PCR or western blot. in vivo experiments were conducted in syngeneic BALB/c mice. Results: Significant changes in protein and gene expression, including higher expression level of TrkB, were found in cells and laryngeal cancer specimens...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29234409/antcin-h-isolated-from-antrodia-cinnamomea-inhibits-renal-cancer-cell-invasion-partly-through-inactivation-of-fak-erk-c-ebp-%C3%AE-c-fos-mmp-7-pathways
#4
Kun-Yuan Chiu, Tzu-Hsiu Chen, Chi-Luan Wen, Jin-Mei Lai, Chi-Chih Cheng, Hsiang-Chun Liu, Shih-Lan Hsu, Yew-Min Tzeng
Antcin-H, a natural triterpene, is purified from a famous anticancer medicinal mushroom, Antrodia cinnamomea, in Taiwan. This study showed that antcin-H inhibited the growth of human renal carcinoma 786-0 cells; the IC50 value (for 48 h) was 170 μM. Besides, the migration and invasion of 786-0 cells were suppressed by antcin-H under noncytotoxic concentrations (<100 μM); these events were accompanied by inhibition of FAK and Src kinase activities, decrease of paxillin phosphorylation, impairment of lamellipodium formation, and upregulation of TIMPs and downregulation of MMPs, especially MMP-7 expression...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29231907/activated-hgf-c-met-axis-in-head-and-neck-cancer
#5
REVIEW
Levi Arnold, Jonathan Enders, Sufi Mary Thomas
Head and neck squamous cell carcinoma (HNSCC) is a highly morbid disease. Recent developments including Food and Drug Administration (FDA) approved molecular targeted agent's pembrolizumab and cetuximab show promise but did not improve the five-year survival which is currently less than 40%. The hepatocyte growth factor receptor; also known as mesenchymal-epithelial transition factor (c-Met) and its ligand hepatocyte growth factor (HGF) are overexpressed in head and neck squamous cell carcinoma (HNSCC); and regulates tumor progression and response to therapy...
December 12, 2017: Cancers
https://www.readbyqxmd.com/read/29217770/protein-c-receptor-stimulates-multiple-signaling-pathways-in-breast-cancer-cells
#6
Daisong Wang, Chunye Liu, Jingqiang Wang, Yingying Jia, Xin Hu, Hai Jiang, Zhi-Ming Shao, Yi Arial Zeng
The protein C receptor (PROCR) has emerged as a stem cell marker in several normal tissues and has also been implicated in tumor progression. However, the functional role of PROCR and the signaling mechanisms downstream of PROCR remain poorly understood. Here, we dissected the PROCR signaling pathways in breast cancer cells. Combining protein array, knockdown, and overexpression methods, we found that PROCR concomitantly activates multiple pathways. We also noted that PROCR-dependent ERK and PI3k-Akt-mTOR signaling pathways proceed through Src kinase and trans-activation of insulin-like growth factor 1 receptor (IGF-1R)...
December 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29137326/overexpression-of-carbonic-anhydrase-ix-induces-cell-motility-by-activating-matrix-metalloproteinase-9-in-human-oral-squamous-cell-carcinoma-cells
#7
Jia-Sin Yang, Chiao-Wen Lin, Yi-Hsien Hsieh, Ming-Hsien Chien, Chun-Yi Chuang, Shun-Fa Yang
Oral cancer is a solid malignant tumor that is prone to occur following hypoxia. There are no clear studies showing a link between hypoxia and oral carcinogenesis. Carbonic anhydrase IX (CAIX), which is a hypoxia-induced transmembrane protein, is highly expressed in various types of human cancer. However, the effects of CAIX on the metastasis of human oral cancer cells and the underlying molecular mechanisms have not been clarified. In this study, we observed that CAIX overexpression increased the migratory and invasive abilities of SCC-9 and SAS cells...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29125118/research-advances-of-calcium-and-integrin-binding-protein-1-in-tumors
#8
Ling Hui, Fang Wang
Calcium-and integrin-binding protein 1(CIB1),a member of calcium binding protein containing EF-hand domain,has been shown to bind a variety of signaling proteins. Interaction of CIB1 with its various binding partners provides valuable insight into potential mechanisms by which CIB1 may regulate diverse tumors characteristic biological process that range from adhesion,migration,cell survival,proliferation,and angiogenesis. CIB1 has also been implicated in both the increase and decrease of cell proliferation...
October 30, 2017: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/29079189/upregulation-of-pag1-cbp-contributes-to-adipose-derived-mesenchymal-stem-cells-promoted-tumor-progression-and-chemoresistance-in-breast-cancer
#9
Yunshu Lu, Yipeng Yang, Yan Liu, Yajuan Hao, Yijian Zhang, Yunping Hu, Lin Jiang, Yurong Gong, Kejin Wu, Yingbin Liu
C-terminal Src kinase (Csk)-binding protein (Cbp) is a ubiquitously expressed transmembrane adaptor protein which regulating Src family kinase (SFK) activities. Although SFKs are well known for their involvement in breast cancer, the function of Cbp in breast carcinogenesis upon the adipose-tumor microenvironment has not been investigated. Here, we reported that adipose-derived mesenchymal stem cells (ASCs) induced increased expression of Cbp accompanied by enhanced cell proliferation and chemotherapy resistance in breast cancer cell MCF-7/ADR...
October 24, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29061800/cytotoxic-effect-of-nano-sio2-in-human-breast-cancer-cells-via-modulation-of-egfr-signaling-cascades
#10
Donghwan Jeon, Hyungjoo Kim, Keesoo Nam, Sunhwa Oh, Seog-Ho Son, Incheol Shin
BACKGROUND/AIM: Silica nanoparticles (nano-SiO2) are widely used in many industrial areas and there is much controversy surrounding cytotoxic effects of such nanoparticles. In order to determine the toxicity and possible molecular mechanisms involved, we conducted several tests with two breast cancer cell lines, MDA-MB-231 and Hs578T. MATERIALS AND METHODS: After exposure to nano-SiO2, growth, apoptosis, motility of breast cancer cells were monitored. In addition, modulation of signal transduction induced by nano-SiO2 was detected through western blot analysis...
November 2017: Anticancer Research
https://www.readbyqxmd.com/read/29034995/mir-1-suppresses-the-proliferation-and-promotes-the-apoptosis-of-esophageal-carcinoma-cells-by-targeting-src
#11
Zhicong Liao, Xiaojun Wang, Hongwei Liang, Ao Yu, Uzair Ur Rehman, Qian Fan, Yue Hu, Chen Wang, Zhen Zhou, Tao Wang
Nonreceptor tyrosine kinase c-Src, also known as Src, is a potent oncogene involved in a series of biological processes including cell growth, differentiation, and apoptosis; however, its expression pattern and function in esophageal cancer is poorly addressed. In this study, abnormal overexpression of Src protein was observed in esophageal cancer tissues, which fuelled the speculation that microRNA-mediated posttranscriptional regulatory mechanism might be involved. Bioinformatic analyses were applied to identify miRNAs that could potentially target Src...
October 16, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29032182/catalpol-suppresses-osteosarcoma-cell-proliferation-through-blocking-epithelial-mesenchymal-transition-emt-and-inducing-apoptosis
#12
Lei Wang, Gui-Bin Xue
Catalpol, an iridoid glucoside compound, is reported to possess diverse pharmacological actions. However, its effects on osteosarcoma are little to be known. In the present study, we showed that catalpol could strongly suppress osteosarcoma progression. Catalpol dose-dependently reduced the cancer cell viability. The migration of osteosarcoma cells was also consistently suppressed by catalpol treatment using the wound healing and transwell migration analysis. Catalpol reduced the expressions of Kras, receptor for activated C-kinase 1(RACK1) and matrix metalloproteinase (MMP)-2 in a dose-dependent manner, revealing the blockage of migration...
October 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28974561/crk-tyrosine-phosphorylation-regulates-pdgf-bb-inducible-src-activation-and-breast-tumorigenicity-and-metastasis
#13
Sushil Kumar, Bin Lu, Viralkumar Davra, Peter Hornbeck, Kazuya Machida, Raymond B Birge
The activity of Src family kinases (Src being the prototypical member) is tightly regulated by differential phosphorylation on Tyr416 (positive) and Tyr527 (negative), a duet that reciprocally regulates kinase activity. The latter negative regulation of Src on Tyr527 is mediated by C-terminal Src kinase (CSK) that phosphorylates Tyr527 and maintains Src in a clamped negative regulated state by promoting an intra-molecular association. Here it is demonstrated that the SH2- and SH3-domain containing adaptor protein CrkII, by virtue of its phosphorylation on Tyr239, regulates the Csk/Src signaling axis to control Src activation...
October 3, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28945796/cabozantinib-and-dastinib-exert-anti-tumor-activity-in-alveolar-soft-part-sarcoma
#14
Kenta Mukaihara, Yu Tanabe, Daisuke Kubota, Keisuke Akaike, Takuo Hayashi, Kaoru Mogushi, Masaki Hosoya, Shingo Sato, Eisuke Kobayashi, Taketo Okubo, Youngji Kim, Shinji Kohsaka, Tsuyoshi Saito, Kazuo Kaneko, Yoshiyuki Suehara
BACKGROUND: Alveolar soft part sarcoma (ASPS) is an extremely rare metastatic soft tissue tumor with a poor prognosis for which no effective systemic therapies have yet been established. Therefore, the development of novel effective treatment approaches is required. Tyrosine kinases (TKs) are being increasingly used as therapeutic targets in a variety of cancers. The purpose of this study was to identify novel therapeutic target TKs and to clarify the efficacy of TK inhibitors (TKIs) in the treatment of ASPS...
2017: PloS One
https://www.readbyqxmd.com/read/28940194/a-new-model-system-identifies-epidermal-growth-factor-receptor-human-epidermal-growth-factor-receptor-2-her2-and-her2-human-epidermal-growth-factor-receptor-3-heterodimers-as-potent-inducers-of-oesophageal-epithelial-cell-invasion
#15
Christiane Daniela Fichter, Camilla Maria Przypadlo, Achim Buck, Nicola Herbener, Bianca Riedel, Luisa Schäfer, Hiroshi Nakagawa, Axel Walch, Thomas Reinheckel, Martin Werner, Silke Lassmann
Oesophageal squamous cell carcinomas and oesophageal adenocarcinomas show distinct patterns of ErbB expression and dimers. The functional effects of specific ErbB homodimers or heterodimers on oesophageal (cancer) cell behaviour, particularly invasion during early carcinogenesis, remain unknown. Here, a new cellular model system for controlled activation of epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER2) and EGFR-HER2 or HER2-human epidermal growth factor receptor 3 (HER3) homodimers and heterodimers was studied in non-neoplastic squamous oesophageal epithelial Het-1A cells...
December 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28910941/-effects-of-src-on-cervical-cancer-cells-proliferation-and-apoptosis-through-erk-signal-transduction-pathway
#16
Z C Song, L Ding, Z Y Ren, X S Sun, Q Yang, L Wang, M J Feng, C L Liu, J T Wang
Objective: To explore the effect of Src on cervical cancer cells through ERK signal transduction pathway. Methods: Experimental study was carried out in vitro. Cervical cancer cell lines Hela (HPV-positive) and C33A (HPV-negative) were treated with Src kinase inhibitor PP2. Then, the cell cycle and apoptosis of each group were evaluated by using flow cytometry (FCM). Western blotting and Real-time PCR were used to detect the levels of the expression of ERK 1/2, c-Fos and c-Jun mRNA and protein respectively...
September 10, 2017: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/28852375/schwann-cell-development-maturation-and-regeneration-a-focus-on-classic-and-emerging-intracellular-signaling-pathways
#17
REVIEW
Luca Franco Castelnovo, Veronica Bonalume, Simona Melfi, Marinella Ballabio, Deborah Colleoni, Valerio Magnaghi
The development, maturation and regeneration of Schwann cells (SCs), the main glial cells of the peripheral nervous system, require the coordinate and complementary interaction among several factors, signals and intracellular pathways. These regulatory molecules consist of integrins, neuregulins, growth factors, hormones, neurotransmitters, as well as entire intracellular pathways including protein-kinase A, C, Akt, Erk/MAPK, Hippo, mTOR, etc. For instance, Hippo pathway is overall involved in proliferation, apoptosis, regeneration and organ size control, being crucial in cancer proliferation process...
July 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28774834/role-of-forkhead-box-class-o-proteins-in-cancer-progression-and-metastasis
#18
REVIEW
Chang Geun Kim, Hyemin Lee, Nehal Gupta, Sharavan Ramachandran, Itishree Kaushik, Sangeeta Srivastava, Sung-Hoon Kim, Sanjay K Srivastava
It is now widely accepted that several gene alterations including transcription factors are critically involved in cancer progression and metastasis. Forkhead Box Class O proteins (FoxOs) including FoxO1/FKHR, FoxO3/FKHRL1, FoxO4/AFX and FoxO6 transcription factors are known to play key roles in proliferation, apoptosis, metastasis, cell metabolism, aging and cancer biology through their phosphorylation, ubiquitination, acetylation and methylation. Though FoxOs are proved to be mainly regulated by upstream phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt signaling pathway, the role of FoxOs in cancer progression and metastasis still remains unclear so far...
August 1, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28761355/ergosterol-peroxide-inhibits-ovarian-cancer-cell-growth-through-multiple-pathways
#19
Weiwei Tan, Meihong Pan, Hui Liu, Hequn Tian, Qing Ye, Hongda Liu
Ergosterol peroxide (EP), a sterol derived from medicinal mushrooms, has been reported to exert antitumor activity in several tumor types. However, the role of EP toward ovarian cancer cells has not been investigated. In this study, we analyzed the cytotoxicity of EP in various cell lines representing high-grade serous ovarian cancer and low-grade serous ovarian cancer, respectively. Although EP showed no significant inhibition of the viability of normal ovarian surface epithelial cells, it impaired the proliferation and invasion capacities of tumor cells in a dose-dependent manner...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28754059/disrupting-the-intramolecular-interaction-between-proto-oncogene-c-src-sh3-domain-and-its-self-binding-peptide-ppii-with-rationally-designed-peptide-ligands
#20
Peng Zhou, Shasha Hou, Zhengya Bai, Zhongyan Li, Heyi Wang, Zheng Chen, Yang Meng
Proto-oncogene non-receptor tyrosine protein kinase c-Src has been involved in the development, progression and metastasis of a variety of human cancers. This protein contains two self-binding peptide (SBP) sites separately between the SH3 domain and polyproline-II (PPII) helix and between the SH2 domain and C-terminal phosphorylatable tail (CTPT), which are potential targets of anticancer drugs to regulate the kinase activity. Here, we described an integrated protocol to systematically investigate the structural basis, energetic property and dynamics behaviour of PPII binding to SH3, and to rationally design potent peptide ligands to target the SBP site of SH3-PPII interaction...
July 28, 2017: Artificial Cells, Nanomedicine, and Biotechnology
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