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https://www.readbyqxmd.com/read/28212573/dynamic-variations-in-epithelial-to-mesenchymal-transition-emt-atm-and-slfn11-govern-response-to-parp-inhibitors-and-cisplatin-in-small-cell-lung-cancer
#1
C Allison Stewart, Pan Tong, Robert J Cardnell, Triparna Sen, Lerong Li, Carl M Gay, Fatemah Masrorpour, You Fan, Rasha O Bara, Ying Feng, Yuanbin Ru, Junya Fujimoto, Samrat T Kundu, Leonard E Post, Karen Yu, Yuqiao Shen, Bonnie S Glisson, Ignatio Wistuba, John V Heymach, Don L Gibbons, Jing Wang, Lauren Averett Byers
Small cell lung cancer (SCLC) is one of the most aggressive forms of cancer, with a 5-year survival <7%. A major barrier to progress is the absence of predictive biomarkers for chemotherapy and novel targeted agents such as PARP inhibitors. Using a high-throughput, integrated proteomic, transcriptomic, and genomic analysis of SCLC patient-derived xenografts (PDXs) and profiled cell lines, we identified biomarkers of drug sensitivity and determined their prevalence in patient tumors. In contrast to breast and ovarian cancer, PARP inhibitor response was not associated with mutations in homologous recombination (HR) genes (e...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212565/the-mir-675-5p-regulates-the-progression-and-development-of-pancreatic-cancer-via-the-ubqln1-zeb1-mir200-axis
#2
Jue Wang, Youli Zhang, Hong Wei, Xingxing Zhang, Yan Wu, Aihua Gong, Yu Xia, Wenbing Wang, Min Xu
Pancreatic cancer (PC) is a highly lethal disease due to extensive metastatic lesions. Accumulating evidence suggests that miR-675-5p plays different roles in metastasis through the regulation of epithelial to mesenchymal (EMT) and the mesenchymal to epithelial transitions (MET) in different cancers. ZEB1 promotes the EMT process by controlling the expression of E-cadherin and may have a reciprocal regulation with Ubiquilin1 (UBQLN1) and mir-200 family in cancer progression. In the present study, we showed that decreased expression of miR-675-5p is associated with the enhanced cell proliferation and survival of PC cells, while the increased expression of mir-675-5p shows the opposite one...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212564/s100a7-promotes-the-migration-invasion-and-metastasis-of-human-cervical-cancer-cells-through-epithelial-mesenchymal-transition
#3
Tian Tian, Xukun Li, Zhen Hua, Jianlin Ma, Xiaowei Wu, Zhihua Liu, Hongyan Chen, Zhumei Cui
S100A7 is an EF-hand calcium-binding protein that has been suggested to be implicated in cell proliferation, migration, invasion and tumor metastasis. However, its role in cervical cancer has not yet been fully clarified. The present study used immunohistochemistry analysis of S100A7 in clinical specimens of cervical cancer to show that S100A7 expression was significantly upregulated in cervical cancer tissues compared with normal cervical tissues and S100A7 expression in high grade cervical intraepithelial neoplasm (CIN) was significantly higher than cervical cancer...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212558/ataxin-1-regulates-epithelial-mesenchymal-transition-of-cervical-cancer-cells
#4
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/28212533/upregulation-of-long-non-coding-rna-plncrna-1-promotes-proliferation-and-induces-epithelial-mesenchymal-transition-in-prostate-cancer
#5
Yang Jin, Zilian Cui, Xudong Li, Xunbo Jin, Jian Peng
OBJECTIVE: To confirm that PlncRNA-1 regulates the cell cycle in prostate cancer cells and induces epithelial-mesenchymal transition (EMT) in prostate cancer through the TGF-β1 pathway. RESULTS: PlncRNA-1 and TGF-β1 expression levels were significantly higher in prostate cancer tissues than in normal prostate tissues (P < 0.05) and were significantly positively correlated. TGF-β1, N-cadherin and Cyclin-D1 were downregulated and E-Cadherin was upregulated in LNCAP cells after silencing of PlncRNA-1, as determined by real-time PCR and Western blot...
February 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28209617/loss-of-ndrg2-expression-confers-oral-squamous-cell-carcinoma-with-enhanced-metastatic-potential
#6
Tomohiro Tamura, Tomonaga Ichikawa, Shingo Nakahata, Yudai Kondo, Yuri Tagawa, Kouji Yamamoto, Kentaro Nagai, Takashi Baba, Ryoji Yamaguchi, Mitsuru Futakuchi, Yoshihiro Yamashita, Kazuhiro Morishita
Loss of the tumor suppressor NDRG2 has been implicated in the development of oral squamous cell carcinoma (OSCC), acting by modulating PI3K/AKT-mediated dephosphorylation of PTEN at S380/S382/T383 (STT). Here we show that the majority of OSCC tumors with lymph node metastasis, a major prognostic factor, exhibit high levels of phosphorylated AKT-S473 and PTEN-STT and low levels of NDRG2 expression. In Ndrg2-deficient mice, which develop a wide range of tumors, we developed a model of OSCC by treatment with the tobacco surrogate 4-nitroquinoline-1-oxide (4-NQO)...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28209613/wnt-%C3%AE-catenin-directs-self-renewal-symmetric-cell-division-of-hterthigh-prostate-cancer-stem-cells
#7
Kai Zhang, Yanjing Guo, Xue Wang, Huifang Zhao, Zhongzhong Ji, Chaping Cheng, Li Li, Yuxiang Fang, Dawei Xu, Helen He Zhu, Wei-Qiang Gao
Cancer stem-like cells (CSC) drive cancer progression and recurrence. Self-renewal expansion of CSC is achieved through symmetric cell division, yet how external stimuli affect intracellular regulatory programs of CSC division modes and stemness remains obscure. Here we report that hTERThigh prostate cancer (PCa) cells exhibit CSC properties, including a stem cell-associated gene expression signature, long term tumor-propagating capacity and epithelial-to-mensenchymal transition (EMT). In promoting the self-renewal symmetric division of hTERThigh PCa cells, WNT3a dramatically decreased the ratio of hTERThigh PCa cells undergoing asymmetric division...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28209612/microrna-520f-reverses-epithelial-to-mesenchymal-transition-by-targeting-adam9-and-tgfbr2
#8
Jasmijn Gm van Kampen, Onno van Hooij, Cornelius Fj Jansen, Frank P Smit, Paula I van Noort, Iman J Schultz, Roel Qj Schaapveld, Jack A Schalken, Gerald W Verhaegh
Reversing epithelial-to-mesenchymal transition (EMT) in cancer cells has been widely considered as an approach to combat cancer progression and therapeutic resistance, but a limited number of broadly comprehensive investigations of microRNAs involved in this process have been conducted. In this study, we screened a library of 1120 microRNA for their ability to transcriptionally activate the E-cadherin gene CDH1 in a promoter reporter assay as a measure of EMT reversal. By this approach, we defined miR-520f as a novel EMT-reversing microRNA...
February 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28209128/mir-296-inhibits-the-metastasis-and-epithelial-mesenchymal-transition-of-colorectal-cancer-by-targeting-s100a4
#9
Zheng He, Lianhua Yu, Shiyi Luo, Mingzhen Li, Junbo Li, Qi Li, Yi Sun, Chengbin Wang
BACKGROUND: Dysregulation of microRNAs (miRNAs) is actively involved in the pathogenesis and tumorigenicity of colorectal cancer (CRC). miR-296 was found to play either oncogenic or tumor suppressive role in human cancers. However, the status of miR-296 and its function in CRC remain unknown. METHODS: The expression of miR-296 was confirmed by qRT-PCR in CRC tissues and cells, and its level was altered by corresponding miRNA vectors. Wound healing and Transwall assays were performed to detect the migration and invasion of CRC cells...
February 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28208810/shp2-plays-a-critical-role-in-il-6-induced-emt-in-breast-cancer-cells
#10
Xuan Sun, Jie Zhang, Zhiyong Wang, Wei Ji, Ran Tian, Fei Zhang, Ruifang Niu
Accumulative evidence demonstrates that the protein tyrosine phosphatase Shp2 functions as a powerful tumor promoter in many types of cancers. Abnormal expression of Shp2 has been implicated in many human malignancies. Overexpression of Shp2 in cancer tissues is correlated with cancer metastasis, resistance to targeted therapy, and poor prognosis. The well-known function of Shp2 is its positive role in regulating cellular signaling initiated by growth factors and cytokines, including interleukin-6 (IL-6). Several recent studies have shown that Shp2 is required for epithelial-mesenchymal transition (EMT), triggered by growth factors...
February 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208648/n-butylidenephthalide-regulated-tumor-stem-cell-genes-ezh2-axl-and-reduced-its-migration-and-invasion-in-glioblastoma
#11
Ssu-Yin Yen, Hong-Meng Chuang, Mao-Hsuan Huang, Shinn-Zong Lin, Tzyy-Wen Chiou, Horng-Jyh Harn
Glioblastoma (GBM) is one of the most common and aggressive types of brain tumor. Due to its highly recurrent rate and poor prognosis, the overall survival time with this type of tumor is only 20-21 months. Recent knowledge suggests that its recurrence is in part due to the presence of cancer stem cells (CSCs), which display radioresistant, chemoresistant, self-renewal and tumorigenic potential. Enhancers of Zeste 2 (EZH2) and AXL receptor tyrosine kinase (AXL) are both highly expressed in GBM. Additionally, they are an essential regulator involved in CSCs maintenance, migration, invasion, epithelial-to-mesenchymal transition (EMT), stemness, metastasis and patient survival...
February 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28207769/role-of-glycogen-synthase-kinase-3%C3%AE-and-ppar-%C3%AE-on-epithelial-to-mesenchymal-transition-in-dss-induced-colorectal-fibrosis
#12
Jacopo Di Gregorio, Roberta Sferra, Silvia Speca, Antonella Vetuschi, Caroline Dubuquoy, Pierre Desreumaux, Simona Pompili, Loredana Cristiano, Eugenio Gaudio, Vincenzo Flati, Giovanni Latella
BACKGROUND: Intestinal fibrosis is characterized by abnormal production and deposition of extracellular matrix (ECM) proteins by activated myofibroblasts. The main progenitor cells of activated myofibroblasts are the fibroblasts and the epithelial cells, the latter through the epithelial-mesenchymal transition (EMT). AIM: To evaluate the action of the new PPAR-γ modulator, GED-0507-34 Levo (GED) on the expression of EMT associated and regulatory proteins such as TGF-β, Smad3, E-cadherin, Snail, ZEB1, β-catenin, and GSK-3β, in a mouse model of DSS-induced intestinal fibrosis...
2017: PloS One
https://www.readbyqxmd.com/read/28207739/overexpression-of-notch-regulated-ankyrin-repeat-protein-is-associated-with-papillary-thyroid-carcinoma-progression
#13
Mingdi Zhang, Yiyu Qin, Bin Zuo, Wei Gong, Shenglai Zhang, Yurong Gong, Zhiwei Quan, Bingfeng Chu
Papillary thyroid cancer (PTC) is one of the endocrine cancers with high clinical and genetic heterogeneity. NOTCH signaling and its downstream NOTCH-Regulated Ankyrin Repeat Protein (NRARP) have been implicated in oncogenesis of many cancers, but the roles in PTCs are less studied. In this study, we show that NRARP is frequently over-expressed in thyroid carcinoma. The over-activation of NRARP is highly and positively correlated with NOTCH genes. Moreover, we find that the expression of NRARP is highly associated with several epithelial mesenchymal transition (EMT) markers and contributes to poor survival outcomes...
2017: PloS One
https://www.readbyqxmd.com/read/28205534/trim14-regulates-cell-proliferation-and-invasion-in-osteosarcoma-via-promotion-of-the-akt-signaling-pathway
#14
Guoxing Xu, Yongfei Guo, Dabo Xu, Yi Wang, Yafeng Shen, Feifei Wang, Yuanyuan Lv, Fanglong Song, Dawei Jiang, Yinquan Zhang, Yi Lou, Yake Meng, Yongji Yang, Yifan Kang
Recent studies have shown that some members of the tripartite motif-containing protein (TRIM) family serve as important regulators of tumorigenesis. However, the biological role of TRIM14 in osteosarcoma remains to be established. In this study, we showed that TRIM14 is upregulated in human osteosarcoma specimens and cell lines, and correlated with osteosarcoma progression and shorter patient survival times. Functional studies demonstrated that overexpression of TRIM14 enhances osteosarcoma cell proliferation, clone formation, cell cycle procession, migration and invasion in vitro and promotes tumor growth in vivo, and conversely, its silencing has the opposite effects...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203609/zeb2-inhibiting-the-inhibitors-in-schwann-cells
#15
Bastian G Brinkmann, Susanne Quintes
Development of Schwann cells is tightly regulated by concerted action of activating and inhibiting factors. Most of the regulatory feedback loops identified to date are transcriptional activators promoting induction of genes coding for integral myelin proteins and lipids. The mechanisms by which inhibitory factors are silenced during Schwann cell maturation are less well understood. We could recently show a pivotal function for the transcription factor zinc finger E-box binding homeobox 2 (Zeb2) during Schwann cell development and myelination as a transcriptional repressor of maturation inhibitors...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28203261/curcumin-suppresses-intestinal-fibrosis-by-inhibition-of-ppar%C3%AE-mediated-epithelial-mesenchymal-transition
#16
Su Xu, Bin Jiang, Hui Wang, Cunsi Shen, Hao Chen, Li Zeng
Intestinal fibrotic stricture is a major complication of Crohn's disease (CD) and epithelial-to-mesenchymal transition (EMT) is considered as an important contributor to the formation of intestinal fibrosis by increasing extracellular matrix (ECM) proteins. Curcumin, a compound derived from rhizomes of Curcuma, has been demonstrated with a potent antifibrotic effect. However, its effect on intestinal fibrosis and the potential mechanism is not completely understood. Here we found that curcumin pretreatment significantly represses TGF-β1-induced Smad pathway and decreases its downstream α-smooth muscle actin (α-SMA) gene expression in intestinal epithelial cells (IEC-6); in contrast, curcumin increases expression of E-cadherin and peroxisome proliferator-activated receptor γ (PPARγ) in IEC-6...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28202676/harnessing-the-bmp-signaling-pathway-to-control-the-formation-of-cancer-stem-cells-by-effects-on-epithelial-to-mesenchymal-transition
#17
REVIEW
Ashish Bosukonda, William D Carlson
Cancer stem cells (CSCs) persist in tumors as a distinct population and may be causative in metastasis and relapse. CSC-rich tumors are associated with higher rates of metastasis and poor patient prognosis. Targeting CSCs therapeutically is challenging, since they seem to be resistant to standard chemotherapy. We have shown that a novel peptide agonist of bone morphogenetic protein (BMP) signaling, P123, is capable of inhibiting the growth of primary tumor cells by interacting with type I receptors selectively [activin receptor-like kinase 2 (ALK2) and ALK3, but not ALK6] and type II BMP receptors, activating SMAD 1/5/8 signaling and controlling the cell cycle pathway...
February 8, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28202525/oncogenic-effects-of-high-mapk-activity-in-colorectal-cancer-mark-progenitor-cells-and-persist-irrespective-of-ras-mutations
#18
Cristina Blaj, Eva Marina Schmidt, Sebastian Lamprecht, Heiko Hermeking, Andreas Jung, Thomas Kirchner, David Horst
About 40% of colorectal cancers have mutations in KRAS accompanied by downstream activation of MAPK signaling which promotes tumor invasion and progression. Here we report that MAPK signaling shows strong intratumoral heterogeneity and unexpectedly remains regulated in colorectal cancer irrespective of KRAS mutation status. Using primary colorectal cancer tissues, xenograft models and MAPK reporter constructs, we showed that tumor cells with high MAPK activity resided specifically at the leading tumor edge, ceased to proliferate, underwent epithelial-mesenchymal transition (EMT), and expressed markers related to colon cancer stem cells...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28202352/amino-acid-transporter-slc38a3-promotes-metastasis-of-non-small-cell-lung-cancer-cells-by-activating-pdk1
#19
Yanhui Wang, Li Fu, Minqing Cui, Yongbin Wang, Yan Xu, Molin Li, Jun Mi
BACKGROUND: Tumor metastasis is a finely-tuned pathological process coupled to metabolic reprogramming that includes both glutamine and glucose. The solute carrier SLC38A3, a member of amino acid/polyamine/organocation (APC) superfamily, is an L-glutamine transporter. It is not clear whether SLC38A3 involves the metastasis of NSCLC (non small cell lung cancer). METHODS: The scratch test and transwell assay were used to determine the ability of NSCLC to migrate. Cellular amino acids content was determined by mass spectrometry...
February 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28201871/a-targeted-contrast-agent-specific-to-an-oncoprotein-in-tumor-microenvironment-with-the-potential-for-detection-and-risk-stratification-of-prostate-cancer-with-mri
#20
Zheng Han, Yajuan Li, Sarah Roelle, Zhuxian Zhou, Yuchi Liu, Rob Sabatelle, Aidan DeSanto, Xin Yu, Hui Zhu, Cristina Magi-Galluzzi, Zheng-Rong Lu
Accurate detection and risk stratification are paramount to the clinical management of prostate cancer. Current diagnostic methods, including prostate specific antigen (PSA) screening, are unable to differentiate high-risk tumors from low-risk tumors, resulting in overdiagnosis and overtreatment of numerous patients. A peptide targeted contrast agent, ZD2-Gd(HP-DO3A), specific to an oncoprotein in tumor microenvironment, EDB-FN, was synthesized for non-invasive detection and characterization of aggressive prostate cancer...
February 16, 2017: Bioconjugate Chemistry
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