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https://www.readbyqxmd.com/read/28214899/therapeutic-targeting-of-epithelial-plasticity-programs-focus-on-the-epithelial-mesenchymal-transition
#1
Reem Malek, Hailun Wang, Kekoa Taparra, Phuoc T Tran
Mounting data points to epithelial plasticity programs such as the epithelial-mesenchymal transition (EMT) as clinically relevant therapeutic targets for the treatment of malignant tumors. In addition to the widely realized role of EMT in increasing cancer cell invasiveness during cancer metastasis, the EMT has also been implicated in allowing cancer cells to avoid tumor suppressor pathways during early tumorigenesis. In addition, data linking EMT to innate and acquired treatment resistance further points towards the desire to develop pharmacological therapies to target epithelial plasticity in cancer...
2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/28214294/ptk6-localized-at-the-plasma-membrane-promotes-cell-proliferation-and-migration-through-phosphorylation-of-eps8
#2
Won-Sik Shin, Hyun Jae Shim, Young Hun Lee, Minju Pyo, Jun Sang Park, So Yun Ahn, Seung-Taek Lee
Protein tyrosine kinase 6 (PTK6; also known as Brk) is closely related to the Src family kinases, but lacks a membrane-targeting myristoylation signal. Sublocalization of PTK6 at the plasma membrane enhances its oncogenic potential. To understand the mechanism(s) underlying the oncogenic property of plasma-membrane-associated PTK6, proteins phosphorylated by membrane-targeted myristoylated PTK6 (Myr-PTK6) were enriched and analyzed using a proteomics approach. Eps8 which was identified by this method is phosphorylated by Myr-PTK6 in HEK293 cells...
February 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28214218/implication-of-downregulation-and-prospective-pathway-signaling-of-microrna-375-in-lung-squamous-cell-carcinoma
#3
Wen-Jie Chen, Ting-Qing Gan, Hui Qin, Su-Ning Huang, Li-Hua Yang, Ye-Ying Fang, Zu-Yun Li, Lin-Jiang Pan, Gang Chen
BACKGROUND: Lung cancer is one of the most typical cancers in the world. Altered expression profiles of microRNA-375(miR-375) are linked to many diseases including lung cancer. However, the relationship between miR-375 and lung squamous cell carcinoma (LUSC) is controversial. METHODS: We first evaluated the 23 LUSCs and the paired normal lung tissues by qRT-PCR. Then we analyzed the LUSC samples with miR-375 expression based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO)...
January 22, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28213656/dual-functional-microrna-186-5p-targets-both-fgf2-and-rela-to-suppress-tumorigenesis-of-glioblastoma-multiforme
#4
Fachen Wang, Hui Jiang, Shanjun Wang, Bing Chen
Glioblastoma multiforme (GBM) is one of the most malignant cancers. MicroRNAs (miRs) were reported to play important roles in GBM recently. However, the role of a novel miR-186-5p in GBM tumorigenesis is still elusive. Using bioinformatics, miR-186-5p was identified as potential regulators of both fibroblast growth factor (FGF)-2 and NF-κB subunit RelA. Luciferase reporter assay was used to confirm the direct recognition FGF2 and RelA mRNAs by miR-186-5p. Invasion and migration assays were employed to study the effect of miR-186-5p on GBM cell growth in vitro...
February 17, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28212727/mitophagy-link-to-cancer-development-and-therapy
#5
REVIEW
Andrey V Kulikov, Ekaterina A Luchkina, Vladimir Gogvadze, Boris Zhivotovsky
Mitophagy, the selective degradation of mitochondria via the autophagic pathway, is a vital mechanism of mitochondrial quality control in cells. Mitophagy is responsible for the removal of malfunctioning or damaged mitochondria, which is essential for normal cellular physiology and tissue development. Pathways involved in the regulation of mitophagy, tumorigenesis, and cell death are overlapping in many cases and may be triggered by common upstream signals, which converge at the mitochondria. The failure to properly modulate mitochondrial turnover in response to oncogenic stresses can either stimulate or suppress tumorigenesis...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28212585/atm-mapk7-crosstalk-in-cancer
#6
EDITORIAL
José Yélamos
News on: Absence of ERK5/MAPK7 delays tumorigenesis in Atm-/- mice by Granados-Jaén, et al. Oncotarget. 2016; 7(46):74435-74447. doi: 10.18632/oncotarget.12908.
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212576/galectin-1-knockdown-improves-drug-sensitivity-of-breast-cancer-by-reducing-p-glycoprotein-expression-through-inhibiting-the-raf-1-ap-1-signaling-pathway
#7
Fang Wang, Pengwei Lv, Yuanting Gu, Lin Li, Xin Ge, Guangcheng Guo
Galectin-1 (Gal-1), a member of the galectin family of carbohydrate binding proteins, plays a pivotal role in various cellular processes of tumorigenesis. The regulatory effect of Gal-1 on multidrug resistance (MDR) breast cancer cells is still unclear. qRT-PCR and western blot showed that Gal-1 and MDR gene 1 (MDR1) were both highly expressed in breast tumor tissues and cell lines. MTT assay and flow cytometry revealed that Gal-1 knockdown improved sensitivity to paclitaxel (PTX) and adriamycin (ADR) in MCF-7/PTX and MCF-7/ADR cells via inhibition of cell viability and promotion of cell apoptosis, while MDR1 overexpression weakened the sensitivity to PTX and ADR induced by Gal-1 knockdown...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212558/ataxin-1-regulates-epithelial-mesenchymal-transition-of-cervical-cancer-cells
#8
A-Ram Kang, Hyoung-Tae An, Jesang Ko, Seongman Kang
The mutant form of the protein ataxin-1 (ATXN1) causes the neurodegenerative disease spinocerebellar ataxia type-1. Recently, ATXN1 was reported to enhance E-cadherin expression in the breast cancer cell line MCF-7, suggesting a potential association between ATXN1 and cancer development. In the present study, we discovered a novel mechanism through which ATXN1 regulates the epithelial-mesenchymal transition (EMT) of cancer cells. Hypoxia-induced upregulation of the Notch intracellular domain expression decreased ATXN1 expression via MDM2-associated ubiquitination and degradation...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212313/chemoprevention-of-rat-mammary-carcinogenesis-by-apiaceae-spices
#9
Farrukh Aqil, Jeyaprakash Jeyabalan, Radha Munagala, Srivani Ravoori, Manicka V Vadhanam, David J Schultz, Ramesh C Gupta
Scientific evidence suggests that many herbs and spices have medicinal properties that alleviate symptoms or prevent disease. In this study, we examined the chemopreventive effects of the Apiaceae spices, anise, caraway, and celery seeds against 17β-estrogen (E2)-mediated mammary tumorigenesis in an ACI (August-Copenhagen Irish) rat model. Female ACI rats were given either control diet (AIN 93M) or diet supplemented with 7.5% (w/w) of anise, caraway, or celery seed powder. Two weeks later, one half of the animals in each group received subcutaneous silastic implants of E2...
February 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212276/preventive-effects-of-pentoxifylline-on-the-development-of-colonic-premalignant-lesions-in-obese-and-diabetic-mice
#10
Kazufumi Fukuta, Yohei Shirakami, Akinori Maruta, Koki Obara, Soichi Iritani, Nobuhiko Nakamura, Takahiro Kochi, Masaya Kubota, Hiroyasu Sakai, Takuji Tanaka, Masahito Shimizu
Obesity and its related metabolic abnormalities, including enhanced oxidative stress and chronic inflammation, are closely related to colorectal tumorigenesis. Pentoxifylline (PTX), a methylxanthine derivative, has been reported to suppress the production of tumor necrosis factor (TNF)-α and possess anti-inflammatory properties. The present study investigated the effects of PTX on the development of carcinogen-induced colorectal premalignant lesions in obese and diabetic mice. Male C57BL/KsJ-db/db mice, which are severely obese and diabetic, were administered weekly subcutaneous injections of the colonic carcinogen azoxymethane (15 mg/kg body weight) for four weeks and then received drinking water containing 125 or 500 ppm PTX for eight weeks...
February 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28211798/serum-microrna-376-family-as-diagnostic-and-prognostic-markers-in-human-gliomas
#11
Qing Huang, Changjiang Wang, Ziming Hou, Gang Wang, Jianghua Lv, Hao Wang, Jun Yang, Zhe Zhang, Hongbing Zhang
BACKGROUND: MicroRNA (miR)-376 family play crucial roles in cancer formation and progression. OBJECTIVE: To investigate expression patterns of circulating miR-376 members in glioma patients, and to explore their diagnostic and prognostic values. METHODS: Expression of miR-376 members in serum samples from 100 glioma patients and 50 healthy controls were detected by quantitative real-time PCR. RESULTS: Serum miR-376a, miR-376b and miR-376c in glioma patients were significantly lower than those in healthy controls (all P< 0...
February 3, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28211617/phosphorylation-of-prb-mechanism-for-rb-pathway-inactivation-in-mycn-amplified-retinoblastoma
#12
Kathryn G Ewens, Tricia R Bhatti, Kimberly A Moran, Jennifer Richards-Yutz, Carol L Shields, Ralph C Eagle, Arupa Ganguly
A small, but unique subgroup of retinoblastoma has been identified with no detectable mutation in the retinoblastoma gene (RB1) and with high levels of MYCN gene amplification. This manuscript investigated alternate pathways of inactivating pRb, the encoded protein in these tumors. We analyzed the mutation status of the RB1 gene and MYCN copy number in a series of 245 unilateral retinoblastomas, and the phosphorylation status of pRb in a subset of five tumors using immunohistochemistry. There were 203 tumors with two mutations in RB1 (RB1(-/-) , 83%), 29 with one (RB1(+/-) , 12%) and 13 with no detectable mutations (RB1(+/+) , 5%)...
February 17, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28211476/novel-roles-for-staufen1-in-embryonal-and-alveolar-rhabdomyosarcoma-via-c-myc-dependent-and-independent-events
#13
Tara E Crawford Parks, Kristen A Marcellus, Jonathan Langill, Aymeric Ravel-Chapuis, Jean Michaud, Kyle N Cowan, Jocelyn Côté, Bernard J Jasmin
Rhabdomyosarcoma is the most common soft tissue sarcoma in children and young adults. Rhabdomyosarcomas are skeletal muscle-like tumours that typically arise in muscle beds, and express key myogenic regulatory factors. However, their developmental program remains blocked in the proliferative phase with cells unable to exit the cell cycle to fuse into myotubes. Recently, we uncovered a key role for the RNA-binding protein Staufen1 during myogenic differentiation through the regulation of c-myc translation. Given the known implication of c-myc in rhabdomyosarcoma, we hypothesized in the current work that Staufen1 controls rhabdomyosarcoma tumorigenesis...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211159/dda1-a-novel-oncogene-promotes-lung-cancer-progression-through-regulation-of-cell-cycle
#14
Lin Cheng, Qianmei Yang, Can Li, Lei Dai, Yang Yang, Qingnan Wang, Yu Ding, Junfeng Zhang, Lei Liu, Shuang Zhang, Ping Fan, Xun Hu, Rong Xiang, Dechao Yu, Yuquan Wei, Hongxin Deng
Lung cancer is globally widespread and associated with high morbidity and mortality. DDA1 (DET1 and DDB1 associated 1) was first discovered and registered in the GenBank database by our colleagues. DDA1, an evolutionarily conserved gene, might have significant functions. Recent reports have demonstrated that DDA1 is linked to the ubiquitin-proteasome pathway and facilitates the degradation of target proteins. However, the function of DDA1 in lung cancer was previously unknown. This study aimed to investigate whether DDA1 contributes to tumorigenesis and progression of lung cancer...
February 17, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28210900/false-responses-of-renilla-luciferase-reporter-control-to-nuclear-receptor-tr4
#15
Dongyun Zhang, Sam S Atlasi, Krishna K Patel, Zihao Zhuang, Anthony P Heaney
Renilla luciferase reporter is a widely used internal control in dual luciferase reporter assay system, where its transcription is driven by a constitutively active promoter. However, the authenticity of the Renilla luciferase response in some experimental settings has recently been questioned. Testicular receptor 4 (TR4, also known as NR2C2) belongs to the subfamily 2 of nuclear receptors. TR4 binds to a direct repeat regulatory element in the promoter of a variety of target genes and plays a key role in tumorigenesis, lipoprotein regulation, and central nervous system development...
February 16, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28209925/the-stress-polarity-pathway-ampk-giv-es-protection-against-metabolic-insults
#16
Pradipta Ghosh
Loss of cell polarity impairs organ development and function; it can also serve as one of the first triggers for oncogenesis. In 2006-2007 two groups simultaneously reported the existence of a special pathway for maintaining epithelial polarity in the face of environmental stressors. In this pathway, AMPK, a key sensor of metabolic stress stabilizes tight junctions, preserves cell polarity, and thereby, maintains epithelial barrier functions. Accumulating evidence since has shown that pharmacologic activation of AMPK by Metformin protects the epithelial barrier against multiple environmental and pathological stressful states and suppresses tumorigenesis...
February 15, 2017: Aging
https://www.readbyqxmd.com/read/28209717/autophagy-metabolism-and-cancer
#17
Jessie Yanxiang Guo, Eileen White
Macroautophagy (autophagy hereafter) is a process that collects cytoplasmic components, particularly mitochondria, and degrades them in lysosomes. In mammalian systems, basal autophagy levels are normally low but are profoundly stimulated by starvation and essential for survival. Cancer cells up-regulate autophagy and can be more autophagy-dependent than most normal tissues. Genetic deficiency in essential autophagy genes in tumors in many autochthonous mouse models for cancer reduces tumor growth. In K-ras(G12D)-driven non-small cell lung cancer (NSCLC) and other models, autophagy sustains metabolism and survival...
February 16, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28209614/distinct-interactions-of-ebp1-isoforms-with-fbxw7-elicits-different-functions-in-cancer
#18
Yuli Wang, Pengju Zhang, Yunshan Wang, Panpan Zhan, Chunyan Liu, Jian-Hua Mao, Guangwei Wei
The ErbB3 receptor binding protein EBP1 encodes two alternatively spliced isoforms p48 and p42. While there is evidence of differential roles for these isoforms in tumorigenesis, little is known about their underlying mechanisms. Here we demonstrate that EBP1 isoforms interact with the SCF-type ubiquitin ligase FBXW7 in distinct ways to exert opposing roles in tumorigenesis. EBP1 p48 bound to the WD domain of FBXW7 as an oncogenic substrate of FBXW7. EBP1 p48 binding sequestered FBXW7α to the cytosol, modulating its role in protein degradation and attenuating its tumor suppressor function...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28209511/heparanase-1-induced-shedding-of-heparan-sulfate-from-syndecan-1-in-hepatocarcinoma-cell-facilitates-lymphatic-endothelial-cell-proliferation-via-vegf-c-erk-pathway
#19
Shengjin Yu, Huiming Lv, He Zhang, Yu Jiang, Yu Hong, Rongjun Xia, Qifang Zhang, Weiwei Ju, Lili Jiang, Geng Ou, Jinhui Zhang, Shujing Wang, Jianing Zhang
Heparanase-1/syndecan-1 axis plays critical roles in tumorigenesis and development. The main mechanism includes heparanase-1 (HPA-1) degrades the heparan sulfate chain of syndecan-1 (SDC-1), and the following shedding of heparan sulfate from tumor cell releases and activates SDC-1 sequestered growth factors. However, the significance of Heparanase-1/syndecan-1 axis and its effects on the microenvironment of lymphatic metastasis in hepatocellular carcinogenesis (HCC) procession have not been reported. Herein, we found that HPA-1 could degrade the heparan sulfate on hepatocarcinoma cell surface...
February 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28209205/long-noncoding-agap2-as1-is-activated-by-sp1-and-promotes-cell-proliferation-and-invasion-in-gastric-cancer
#20
Fuzhen Qi, Xianghua Liu, Hao Wu, Xiang Yu, Chenchen Wei, Xiaodan Huang, Guozhong Ji, Fengqi Nie, Keming Wang
BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as important regulators of tumorigenesis and cancer progression. Recently, the lncRNA AGAP2-AS1 was identified as an oncogenic lncRNA in human non-small cell lung cancer (NSCLC) and its elevated expression was linked to NSCLC development and progression. However, the expression pattern and molecular mechanism of AGAP2-AS1 in gastric cancer (GC) have not been characterized. METHODS: Bioinformatic analysis was performed to determine AGAP2-AS1 expression levels in the GC and normal tissues using gene profiling data from the Gene Expression Omnibus...
February 16, 2017: Journal of Hematology & Oncology
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