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https://www.readbyqxmd.com/read/27925454/rap1a-promotes-ovarian-cancer-metastasis-via-activation-of-erk-p38-and-notch-signaling
#1
Lili Lu, Jingshu Wang, Yougen Wu, Ping Wan, Gong Yang
As one of the Ras-associated proteins, Rap1A has been linked to cancer initiation and development. However, the precise function of Rap1A in ovarian cancer is still not understood. Here, we show that Rap1A promotes ovarian cancer tumorigenesis and metastasis via stimulating cell proliferation, migration and invasion both in vivo and in vitro. Mechanistic study showed that Rap1A activates extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK) and Notch pathways, leading to the enhanced expression of several epithelial-mesenchymal transition (EMT) markers such as slug, zeb1, vimentin, fibronectin, and MMP9...
December 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27903989/repression-of-yap-by-nctd-disrupts-nsclc-progression
#2
Jiwei Guo, Yan Wu, Lijuan Yang, Jing Du, Kaikai Gong, Weiwei Chen, Juanjuan Dai, XueLin Li, Sichuan Xi
The efficacy of available lung cancer therapeutic interference is significantly limited by various resistance mechanisms to those drugs. Activation of the oncogene YAP underlying the initiation, progression, and metastasis of lung cancer associates with poor prognosis and confers drug resistance against targeted therapy. In this study, we evaluated the specificity of norcantharidin (NCTD) in repressing YAP to inhibit non-small cell lung carcinoma (NSCLC) progression. Our study revealed that YAP signal pathways were aberrantly activated in lung cancer tissues and cells which rendered more proliferative and invasive phenotypes to human lung cancer cells...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902484/depletion-of-mitochondrial-reactive-oxygen-species-downregulates-epithelial-to-mesenchymal-transition-in-cervical-cancer-cells
#3
Galina Shagieva, Lidiya Domnina, Olga Makarevich, Boris Chernyak, Vladimir Skulachev, Vera Dugina
In the course of cancer progression, epithelial cells often acquire morphological and functional characteristics of mesenchymal cells, a process known as epithelial-to-mesenchymal transition (EMT). EMT provides epithelial cells with migratory, invasive, and stem cell capabilities. Reactive oxygen species produced by mitochondria (mtROS) could be of special importance for pro-tumorigenic signaling and EMT.In our study, we used mitochondria-targeted antioxidant SkQ1 to lower the mtROS level and analyze their role in the regulation of the actin cytoskeleton, adhesion junctions, and signaling pathways critical for tumorigenesis of cervical carcinomas...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27898034/emerging-non-canonical-functions-and-regulation-by-p53-p53-and-stemness
#4
REVIEW
David J Olivos, Lindsey D Mayo
Since its discovery nearly 40 years ago, p53 has ascended to the forefront of investigated genes and proteins across diverse research disciplines and is recognized most exclusively for its role in cancer as a tumor suppressor. Levine and Oren (2009) reviewed the evolution of p53 detailing the significant discoveries of each decade since its first report in 1979. In this review, we will highlight the emerging non-canonical functions and regulation of p53 in stem cells. We will focus on general themes shared among p53's functions in non-malignant stem cells and cancer stem-like cells (CSCs) and the influence of p53 on the microenvironment and CSC niche...
November 26, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27889319/cell-type-specific-chromatin-states-differentially-prime-squamous-cell-carcinoma-tumor-initiating-cells-for-epithelial-to-mesenchymal-transition
#5
Mathilde Latil, Dany Nassar, Benjamin Beck, Soufiane Boumahdi, Li Wang, Audrey Brisebarre, Christine Dubois, Erwin Nkusi, Sandrine Lenglez, Agnieszka Checinska, Alizée Vercauteren Drubbel, Michael Devos, Wim Declercq, Rui Yi, Cédric Blanpain
Epithelial to mesenchymal transition (EMT) in cancer cells has been associated with metastasis, stemness, and resistance to therapy. Some tumors undergo EMT while others do not, which may reflect intrinsic properties of their cell of origin. However, this possibility is largely unexplored. By targeting the same oncogenic mutations to discrete skin compartments, we show that cell-type-specific chromatin and transcriptional states differentially prime tumors to EMT. Squamous cell carcinomas (SCCs) derived from interfollicular epidermis (IFE) are generally well differentiated, while hair follicle (HF) stem cell-derived SCCs frequently exhibit EMT, efficiently form secondary tumors, and possess increased metastatic potential...
November 16, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27878502/emt-cell-plasticity-and-metastasis
#6
Christine L Chaffer, Beatriz P San Juan, Elgene Lim, Robert A Weinberg
Carcinoma cells that are induced to suppress their epithelial features and upregulate mesenchymal gene expression programs acquire traits that promote an invasive and metastatic phenotype. This is achieved through the expression of a program termed the epithelial-to-mesenchymal transition (EMT)-a fundamental cell-biological process that plays key roles in embryogenesis and wound healing. Re-activation of the EMT during cancer promotes disease progression and enhances the metastatic phenotype by bestowing upon previously benign carcinoma cell traits such as migration, invasion, resistance to anoikis, chemoresistance and tumour-initiating potential...
November 22, 2016: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/27878304/upregulation-of-mek5-by-stat3-promotes-breast-cancer-cell-invasion-and-metastasis
#7
Fang Liu, Hao Zhang, Hui Song
Mitogen extracellular-signal-regulated kinase kinase 5 (MEK5) plays an important role in promoting cell proliferation and tumorigenesis. The aberrant expression of MEK5 has been reported in various malignant diseases including cancers of breast, prostate, lung, colorectal and brain. However, the function and regulation of MEK5 signaling pathway are ambiguous and remain elusive with respect to its oncogenic roles in various cancers, especially in the regulation of the initiation and progression of cancer invasion and metastasis...
November 18, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27869652/epithelial-to-mesenchymal-transition-drives-a-pro-metastatic-golgi-compaction-process-through-scaffolding-protein-paqr11
#8
Xiaochao Tan, Priyam Banerjee, Hou-Fu Guo, Stephen Ireland, Daniela Pankova, Young-Ho Ahn, Irodotos Michail Nikolaidis, Xin Liu, Yanbin Zhao, Yongming Xue, Alan R Burns, Jonathon Roybal, Don L Gibbons, Tomasz Zal, Chad J Creighton, Daniel Ungar, Yanzhuang Wang, Jonathan M Kurie
Tumor cells gain metastatic capacity through a Golgi phosphoprotein 3-dependent (GOLPH3-dependent) Golgi membrane dispersal process that drives the budding and transport of secretory vesicles. Whether Golgi dispersal underlies the pro-metastatic vesicular trafficking that is associated with epithelial-to-mesenchymal transition (EMT) remains unclear. Here, we have shown that, rather than causing Golgi dispersal, EMT led to the formation of compact Golgi organelles with improved ribbon linking and cisternal stacking...
November 21, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27863449/il6-mediated-inflammatory-loop-reprograms-normal-to-emt-metastatic-cscs-in-pre-neoplastic-liver-of-tgf%C3%AE-deficient-%C3%AE-2sp-mice
#9
Abhisek Mitra, Jun Yan, Xueqing Xia, Shouhao Zhou, Jian Chen, Lopa Mishra, Shulin Li
Hepatocellular carcinoma (HCC) is the second-leading cause of cancer-related deaths world-wide with poor survival rate. As many as 40% of HCCs are clonal, with alteration of key tumor suppressor pathways in stem cells is the primary cause of HCC initiation. However, mechanisms that generate metastatic stem cells in pre-neoplastic liver tissue are not well understood. We hypothesized that chronic inflammation is a major driver of the transformation of genetically defective liver stem cells (LSCs) into highly metastatic liver cancer cells in premalignant liver tissue...
November 18, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27862841/the-ubiquitin-ligase-ube4a-inhibits-prostate-cancer-progression-by-targeting-interleukin-like-emt-inducer-ilei
#10
Yanan Sun, Xiaopeng Jia, Qiang Gao, Xing Liu, Lianguo Hou
Epithelial to mesenchymal transition (EMT) is an important prerequisite for metastasis to secondary organs. Interleukin-like EMT inducer (ILEI) protein has been shown to translationally upregulated during EMT and metastatic progression as a consequence of aberrant TGF-β signaling. Our initial evaluation of FAM3C (encoding ILEI) and ILEI expression in normal prostate (PCS-440-010) and prostate cancer cell lines (DU145, LNCaP, and PC3) revealed detectable protein expression in only LNCaP cell line even though all cell lines tested had comparable FAM3C expression...
November 10, 2016: IUBMB Life
https://www.readbyqxmd.com/read/27845427/role-of-thioredoxin-reductase-1-in-dysplastic-transformation-of-human-breast-epithelial-cells-triggered-by-chronic-oxidative-stress
#11
Chaoran Dong, Lei Zhang, Ruoxuan Sun, Jianying Liu, Hanwei Yin, Xiaoxiao Li, Xiaoqing Zheng, Huihui Zeng
Thioredoxin reductase 1 (TrxR1) is a pivotal intracellular redox sensor and antioxidant enzyme. On the other hand, overexpression of TrxR1 is closely correlated with the initiation of various tumors including breast cancer, though the detailed mechanism remains unclear. Here we investigated the role of TrxR1 in dysplastic transformation of human breast epithelial cell line MCF-10A induced by chronic oxidative stress. Not surprisingly, sustained exposure to H2O2 significantly augmented the expression and activity of TrxR1 in MCF-10A cells...
November 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27835580/ky1022-a-small-molecule-destabilizing-ras-via-targeting-the-wnt-%C3%AE-catenin-pathway-inhibits-development-of-metastatic-colorectal-cancer
#12
Yong-Hee Cho, Pu-Hyeon Cha, Saluja Kaduwal, Jong-Chan Park, Sang-Kyu Lee, Jeong-Soo Yoon, Wookjin Shin, Hyuntae Kim, Eun Ji Ro, Kyung-Hwa Koo, Ki-Sook Park, Gyoonhee Han, Kang-Yell Choi
APC (80-90%) and K-Ras (40-50%) mutations frequently occur in human colorectal cancer (CRC) and these mutations cooperatively accelerate tumorigenesis including metastasis. In addition, both β-catenin and Ras levels are highly increased in CRC, especially in metastatic CRC (mCRC). Therefore, targeting both the Wnt/β-catenin and Ras pathways could be an ideal therapeutic approach for treating mCRC patients. In this study, we characterized the roles of KY1022, a small molecule that destabilizes both β-catenin and Ras via targeting the Wnt/β-catenin pathway, in inhibiting the cellular events, including EMT, an initial process of metastasis, and apoptosis...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27815674/epithelial-plasticity-during-human-breast-morphogenesis-and-cancer-progression
#13
REVIEW
Saevar Ingthorsson, Eirikur Briem, Jon Thor Bergthorsson, Thorarinn Gudjonsson
Understanding the complex events leading to formation of an epithelial-based organ such as the breast requires a detailed insight into the crosstalk between epithelial and stromal compartments. These interactions occur both through heterotypic cellular interactions and between cells and matrix components. While in vivo models may partially capture these complex interactions, there is a need for in- vitro models to study these events. In this review we discuss cell-cell interactions in breast development focusing on the stem cell niche and branching morphogenesis...
November 4, 2016: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/27812180/comparative-gene-expression-profiling-of-primary-and-metastatic-renal-cell-carcinoma-stem-cell-like-cancer-cells
#14
Mohammed I Khan, Anna M Czarnecka, Sławomir Lewicki, Igor Helbrecht, Klaudia Brodaczewska, Irena Koch, Robert Zdanowski, Magdalena Król, Cezary Szczylik
BACKGROUND: Recent advancement in cancer research has shown that tumors are highly heterogeneous, and multiple phenotypically different cell populations are found in a single tumor. Cancer development and tumor growth are driven by specific types of cells-stem cell-like cancer cells (SCLCCs)-which are also responsible for metastatic spread and drug resistance. This research was designed to verify the presence of SCLCCs in renal cell cancer cell lines. Subsequently, we aimed to characterize phenotype and cell biology of CD105+ cells, defined previously as renal cell carcinoma tumor-initiating cells...
2016: PloS One
https://www.readbyqxmd.com/read/27811360/p16ink4a-suppresses-brca1-deficient-mammary-tumorigenesis
#15
Alexandria Scott, Feng Bai, Ho Lam Chan, Shiqin Liu, Jinshan Ma, Joyce M Slingerland, David J Robbins, Anthony J Capobianco, Xin-Hai Pei
Senescence prevents the proliferation of genomically damaged, but otherwise replication competent cells at risk of neoplastic transformation. p16INK4A (p16), an inhibitor of CDK4 and CDK6, plays a critical role in controlling cellular senescence in multiple organs. Functional inactivation of p16 by gene mutation and promoter methylation is frequently detected in human breast cancers. However, deleting p16 in mice or targeting DNA methylation within the murine p16 promoter does not result in mammary tumorigenesis...
November 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27806322/upregulation-of-long-noncoding-rna-hottip-promotes-metastasis-of-esophageal-squamous-cell-carcinoma-via-induction-of-emt
#16
Xuemei Chen, Hongyu Han, Yuqi Li, Qiongxia Zhang, Kailan Mo, Size Chen
Esophageal squamous cell carcinoma (ESCC) is one of the prevalent and deadly cancers worldwide, especially in Eastern Asia. The prognosis of ESCC remains poor; thus, it is still necessary to further dissect the underlying mechanisms and explore therapeutic targets of ESCC. Recent studies show that lncRNAs involve in the initiation and progression of various cancers including ESCC. HOTTIP has been recently revealed as oncogenic regulator in different cancers, however, whether HOTTIP is involved in ESCC remains poorly understood...
October 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/27785690/small-cell-lung-cancer-an-epithelial-to-mesenchymal-transition-emt-like-cancer-significance-of-inactive-notch-signaling-and-expression-of-achaete-scute-complex-homologue-1
#17
Takaaki Ito, Shinji Kudoh, Takaya Ichimura, Kosuke Fujino, Wael Ahmed Maher Abdo Hassan, Naoko Udaka
Small cell lung cancer (SCLC) is one of the most malignant neoplasms in common human cancers. The tumor is composed of small immature-looking cells with a round or fusiform shape, which possesses weak adhesion features among them, suggesting that SCLC shows the morphological characteristics of epithelial to mesenchymal transition (EMT). SCLC is characterized by high metastatic and recurrent rates, sensitivity to the initial chemotherapy, and easy acquirement of chemoresistance afterwards. These characters may be related to the EMT phenotype of SCLC...
October 26, 2016: Human Cell
https://www.readbyqxmd.com/read/27775688/inhibition-of-nf-kappa-b-pathway-leads-to-deregulation-of-epithelial-mesenchymal-transition-and-neural-invasion-in-pancreatic-cancer
#18
Alice Nomura, Kaustav Majumder, Bhuwan Giri, Patricia Dauer, Vikas Dudeja, Sabita Roy, Sulagna Banerjee, Ashok K Saluja
NF-κB has an essential role in the initiation and progression of pancreatic cancer and specifically mediates the induction of epithelial-mesenchymal transition and invasiveness. In this study, we demonstrate the importance of activated NF-κB signaling in EMT induction, lymphovascular metastasis, and neural invasion. Modulation of NF-κB activity was accomplished through the specific NF-κB inhibitor (BAY 11-7085), triptolide, and Minnelide treatment, as well as overexpression of IKBα repressor and IKK activator plasmids...
December 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27764776/igf-1-contributes-to-the-expansion-of-melanoma-initiating-cells-through-an-epithelial-mesenchymal-transition-process
#19
Vincent Le Coz, Chaobin Zhu, Aurore Devocelle, Aimé Vazquez, Claude Boucheix, Sandy Azzi, Cindy Gallerne, Pierre Eid, Séverine Lecourt, Julien Giron-Michel
Melanoma is a particularly virulent human cancer, due to its resistance to conventional treatments and high frequency of metastasis. Melanomas contain a fraction of cells, the melanoma-initiating cells (MICs), responsible for tumor propagation and relapse. Identification of the molecular pathways supporting MICs is, therefore, vital for the development of targeted treatments. One factor produced by melanoma cells and their microenvironment, insulin-like growth factor-1 (IGF- 1), is linked to epithelial-mesenchymal transition (EMT) and stemness features in several cancers...
October 18, 2016: Oncotarget
https://www.readbyqxmd.com/read/27764163/targeting-epithelial-mesenchymal-transition-for-identification-of-inhibitors-for-pancreatic-cancer-cell-invasion-and-tumor-spheres-formation
#20
Kishore Polireddy, Ruochen Dong, Peter R McDonald, Tao Wang, Brendan Luke, Ping Chen, Melinda Broward, Anuradha Roy, Qi Chen
BACKGROUND: Pancreatic cancer has an enrichment of stem-like cancer cells (CSCs) that contribute to chemoresistant tumors prone to metastasis and recurrence. Drug screening assays based on cytotoxicity cannot identify specific CSC inhibitors, because CSCs comprise only a small portion of cancer cell population, and it is difficult to propagate stable CSC populations in vitro for high-throughput screening (HTS) assays. Based on the important role of cancer cell epithelial-to-mesenchymal transition (EMT) in promoting CSCs, we hypothesized that inhibition of EMT can be a useful strategy for inhibiting CSCs, and therefore a feasible approach for HTS can be built for identification of CSC inhibitors, based on assays detecting EMT inhibition...
2016: PloS One
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