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https://www.readbyqxmd.com/read/29222037/diabetes-as-risk-factor-for-pancreatic-cancer-hyperglycemia-promotes-epithelial-mesenchymal-transition-and-stem-cell-properties-in-pancreatic-ductal-epithelial-cells
#1
Sascha Rahn, Vivien Zimmermann, Fabrice Viol, Hendrike Knaack, Kerstin Stemmer, Lena Peters, Lennart Lenk, Hendrik Ungefroren, Dieter Saur, Heiner Schäfer, Ole Helm, Susanne Sebens
Type 2 diabetes mellitus (T2DM) is associated with hyperglycemia and a risk to develop pancreatic ductal adenocarcinoma (PDAC), one of the most fatal malignancies. Cancer stem cells (CSC) are essential for initiation and maintenance of tumors, and acquisition of CSC-features is linked to epithelial-mesenchymal-transition (EMT). The present study investigated whether hyperglycemia promotes EMT and CSC-features in premalignant and malignant pancreatic ductal epithelial cells (PDEC). Under normoglycemia (5 mM d-glucose), Panc1 PDAC cells but not premalignant H6c7-kras cells exhibited a mesenchymal phenotype along with pronounced colony formation...
December 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29221199/long-non-coding-rna-uca1-indicates-an-unfavorable-prognosis-and-promotes-tumorigenesis-via-regulating-akt-gsk-3%C3%AE-signaling-pathway-in-cholangiocarcinoma
#2
Yi Xu, Yue Yao, Kaiming Leng, Zhenglong Li, Wei Qin, Xiangyu Zhong, Pengcheng Kang, Ming Wan, Xingming Jiang, Yunfu Cui
Long non-coding RNAs (lncRNAs) have been documented to play key roles in a wide range of pathophysiological processes, including cancer initiation and progression. Recently, the aberrant expression of urothelial carcinoma associated 1 (UCA1) was observed in many types of cancers. However, its clinical relevance and exact effects in cholangiocarcinoma (CCA) remains unknown. In the present study, we aimed to investigate the clinical significance of UCA1 and evaluate its prognostic value in patients with CCA. Besides, the functional roles of UCA1 were detected both in vitro and in vivo...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29216625/missing-links-in-epithelial-mesenchymal-transition-long-non-coding-rnas-enter-the-arena
#3
Lei Wang, Fan Yang, Lin-Tao Jia, An-Gang Yang
Cancer metastasis occurs through a series of sequential steps, which involves dissemination of tumor cells from a primary site and colonization in distant tissues. To promote the invasion-metastasis cascade, carcinoma cells usually initiate a cell-biological program called epithelial-mesenchymal transition (EMT), which is orchestrated by a set of master regulators, including TGF-β, Snail, ZEB and Twist families. The biological activities of these molecules are tightly regulated by a variety of cell-intrinsic pathways as well as extracellular cues...
December 6, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29215705/activation-of-fibroblasts-by-nicotine-promotes-the-epithelial-mesenchymal-transition-and-motility-of-breast-cancer-cells
#4
Pin-Cyuan Chen, Wen-Ying Lee, Hsiang-Hsi Ling, Chia-Hsiung Cheng, Ku-Chung Chen, Cheng-Wei Lin
The tumor microenvironment plays an important role in tumor initiation and progression. It is well documented that nicotine participates in cigarette smoking-related malignancies. Previous studies focused on the effects of nicotine on tumor cells; however, the role of the microenvironment in nicotine-mediated tumorigenesis is poorly understood. Herein, we investigated the effect and molecular mechanism of nicotine on fibroblasts and its contribution to breast cancer. We found that nicotine induced the epithelial-mesenchymal transition (EMT) of breast cancer cells and promoted activation of fibroblasts...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29208672/cd271-confers-an-invasive-and-metastatic-phenotype-of-head-and-neck-squamous-cell-carcinoma-through-the-upregulation-of-slug
#5
Man Ki Chung, Young Ho Jung, Joon Kyoo Lee, Soo Youn Cho, Oihana J Murillo-Sauca, Ravindra Uppaluri, June Ho Shin, John B Sunwoo
PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is comprised of heterogeneous populations of cells, and CD271 (NGFR; p75NTR) has been associated with a tumor-initiating cell subpopulation. This study assessed the role of CD271 in modulating metastatic behavior in HNSCC. EXPERIMENTAL DESIGN: CD271 was overexpressed in murine and human oral squamous cell carcinoma cells to assess the impact of CD271 activation on the invasive and metastatic phenotype of these cells, using in vitro and orthotopic in vivo modeling...
December 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29207686/molecular-targeting-of-the-aurora-a-smad5-oncogenic-axis-restores-chemosensitivity-in-human-breast-cancer-cells
#6
Mateusz Opyrchal, Malgorzata Gil, Jeffrey L Salisbury, Mathew P Goetz, Vera Suman, Amy Degnim, James McCubrey, Tufia Haddad, Ianko Iankov, Chenye B Kurokawa, Nicole Shumacher, James N Ingle, Evanthia Galanis, Antonino B D'Assoro
Although the majority of breast cancers initially respond to the cytotoxic effects of chemotherapeutic agents, most breast cancer patients experience tumor relapse and ultimately die because of drug resistance. Breast cancer cells undergoing epithelial to mesenchymal transition (EMT) acquire a CD44+/CD24-/ALDH1+ cancer stem cell-like phenotype characterized by an increased capacity for tumor self-renewal, intrinsic drug resistance and high proclivity to develop distant metastases. We uncovered in human breast tumor xenografts a novel non-mitotic role of Aurora-A kinase in promoting breast cancer metastases through activation of EMT and expansion of breast tumor initiating cells (BTICs)...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207623/isoxazole-compound-ml327-blocks-myc-expression-and-tumor-formation-in-neuroblastoma
#7
Eric J Rellinger, Chandrasekhar Padmanabhan, Jingbo Qiao, Brian T Craig, Hanbing An, Jing Zhu, Hernán Correa, Alex G Waterson, Craig W Lindsley, R Daniel Beauchamp, Dai H Chung
Neuroblastomas are the most common extracranial solid tumors in children and arise from the embryonic neural crest. MYCN-amplification is a feature of ∼30% of neuroblastoma tumors and portends a poor prognosis. Neural crest precursors undergo epithelial-to-mesenchymal transition (EMT) to gain migratory potential and populate the sympathoadrenal axis. Neuroblastomas are posited to arise due to a blockade of neural crest differentiation. We have recently reported effects of a novel MET inducing compound ML327 (N-(3-(2-hydroxynicotinamido) propyl)-5-phenylisoxazole-3-carboxamide) in colon cancer cells...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29190794/3d-collagen-fibrillar-microstructure-guides-pancreatic-cancer-cell-phenotype-and-serves-as-a-critical-design-parameter-for-phenotypic-models-of-emt
#8
T J Puls, Xiaohong Tan, Catherine F Whittington, Sherry L Voytik-Harbin
Pancreatic cancer, one of the deadliest cancers, is characterized by high rates of metastasis and intense desmoplasia, both of which are associated with changes in fibrillar type I collagen composition and microstructure. Epithelial to mesenchymal transition (EMT), a critical step of metastasis, also involves a change in extracellular matrix (ECM) context as cells detach from basement membrane (BM) and engage interstitial matrix (IM). The objective of this work was to develop and apply an in-vitro three-dimensional (3D) tumor-ECM model to define how ECM composition and biophysical properties modulate pancreatic cancer EMT...
2017: PloS One
https://www.readbyqxmd.com/read/29188076/epithelial-to-mesenchymal-transition-in-gallbladder-cancer-from-clinical-evidence-to-cellular-regulatory-networks
#9
REVIEW
Sunwang Xu, Ming Zhan, Jian Wang
Gallbladder cancer (GBC), with late diagnosis, rapid disease progression and early metastasis, is a highly aggressive malignant tumor found worldwide. Patients with GBC have poor survival, low curative resection rates and early recurrence. For such a lethal tumor, uncovering the mechanisms and exploring new strategies to prevent tumor progression and metastasis are critically important. Epithelial-to-mesenchymal transition (EMT) has a prominent role in the early steps of tumor progression and metastasis by initiating polarized epithelial cell transition into motile mesenchymal cells...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/29187638/numb-prevents-a-complete-epithelial-mesenchymal-transition-by-modulating-notch-signalling
#10
Federico Bocci, Mohit K Jolly, Satyendra C Tripathi, Mitzi Aguilar, Samir M Hanash, Herbert Levine, José N Onuchic
Epithelial-mesenchymal transition (EMT) plays key roles during embryonic development, wound healing and cancer metastasis. Cells in a partial EMT or hybrid epithelial/mesenchymal (E/M) phenotype exhibit collective cell migration, forming clusters of circulating tumour cells-the primary drivers of metastasis. Activation of cell-cell signalling pathways such as Notch fosters a partial or complete EMT, yet the mechanisms enabling cluster formation remain poorly understood. Using an integrated computational-experimental approach, we examine the role of Numb-an inhibitor of Notch intercellular signalling-in mediating EMT and clusters formation...
November 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29182685/mir205-inhibits-stem-cell-renewal-in-sum159pt-breast-cancer-cells
#11
Víctor Mayoral-Varo, Annarica Calcabrini, María Pilar Sánchez-Bailón, Jorge Martín-Pérez
miR205 has a dual activity, as tumor suppressor and as oncogene. Here we analyzed the impact of miR205 ectopic expression in the initial tumorigenic processes of SUM159PT, a triple negative breast cancer cell line with low endogenous levels of miR205. In SUM159PT, miR205 inhibited expression of its targets VEGFA, ErbB3, Zeb1, Fyn and Lyn A/B; it reduced cell proliferation, and Myc/cyclin D1 levels, while increased p27kip1 expression. miR205 abolished anchorage-independent growth, inhibited migration and invasion, Src-kinases/Stat3 axis activation, and levels of secreted MMP9...
2017: PloS One
https://www.readbyqxmd.com/read/29180473/new-mechanisms-of-resistance-to-mek-inhibitors-in-melanoma-revealed-by-intravital-imaging
#12
Hailey E Brighton, Steven P Angus, Tao Bo, Jose Roques, Alicia C Tagliatela, David Darr, Kubra Karagoz, Noah Sciaky, Michael Gatza, Norman E Sharpless, Gary L Johnson, James E Bear
Targeted therapeutics that are initially effective in cancer patients nearly invariably engender resistance at some stage, an inherent challenge in the use of any molecular targeted drug in cancer settings. In this study, we evaluated resistance mechanisms arising in metastatic melanoma to MAPK pathway kinase inhibitors, as a strategy to identify candidate strategies to limit risks of resistance. To investigate longitudinal responses, we developed an intravital serial imaging approach that can directly visualize drug response in an inducible RAF-driven, autochthonous murine model of melanoma incorporating a fluorescent reporter allele (tdTomatoLSL)...
November 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/29177029/tumorigenesis-as-a-process-of-gradual-loss-of-original-cell-identity-and-gain-of-properties-of-neural-precursor-progenitor-cells
#13
REVIEW
Ying Cao
Cancer is a complex disease without a unified explanation for its cause so far. Our recent work demonstrates that cancer cells share similar regulatory networks and characteristics with embryonic neural cells. Based on the study, I will address the relationship between tumor and neural cells in more details. I collected the evidence from various aspects of cancer development in many other studies, and integrated the information from studies on cancer cell properties, cell fate specification during embryonic development and evolution...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29176314/elevated-expression-of-zinc-finger-protein-703-promotes-cell-proliferation-and-metastasis-through-pi3k-akt-gsk-3%C3%AE-signalling-in-oral-squamous-cell-carcinoma
#14
Hao Wang, Xubin Deng, Jinshan Zhang, Zhilin Ou, Jiajie Mai, Shangwei Ding, Shaofen Huo
BACKGROUND/AIMS: Zinc finger protein 703 (ZNF703), initially identified as a novel oncogene in human breast cancer, is a member of the NET/NlZ family of zinc finger transcription factors. It is recognized that the overexpression of ZNF703 is associated with various types of human cancers, but the role and molecular mechanism of ZNF703 in oral squamous cell carcinoma (OSCC) are unknown. METHODS: ZNF703 expression levels were examined in OSCC tissues and non-cancerous tissues by qRT-PCR and immunohistochemistry (IHC)...
November 24, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29170132/high-aldh-activity-defines-ovarian-cancer-stem-like-cells-with-enhanced-invasiveness-and-emt-progress-which-are-responsible-for-tumor-invasion
#15
Yiying Li, Tong Chen, Jie Zhu, Haiyan Zhang, Hua Jiang, Hong Sun
Epithelial ovarian cancer (EOC) is highly metastatic and current therapeutics are unsatisfactory. Cancer stem/stem-like cells (CSCs/CSCLs) represent a rare population of undifferentiated oncogenic cells responsible for tumor initiation and maintenance. We identified ovarian cancer ALDH(high) (aldehyde dehydrogenase) population could perform not only strengthened CSCLs properties embodied in colony-formation, CSCs-markers expression, and tumorigenesis in vivo, but also a greater invasive capacity with advanced EMT progress and anti-apoptosis compared with ALDH(low) cells...
November 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29162812/role-of-epithelial-to-mesenchymal-transition-associated-genes-in-mammary-gland-regeneration-and-breast-tumorigenesis
#16
Shaheen S Sikandar, Angera H Kuo, Tomer Kalisky, Shang Cai, Maider Zabala, Robert W Hsieh, Neethan A Lobo, Ferenc A Scheeren, Sopheak Sim, Dalong Qian, Frederick M Dirbas, George Somlo, Stephen R Quake, Michael F Clarke
Previous studies have proposed that epithelial to mesenchymal transition (EMT) in breast cancer cells regulates metastasis, stem cell properties and chemo-resistance; most studies were based on in vitro culture of cell lines and mouse transgenic cancer models. However, the identity and function of cells expressing EMT-associated genes in normal murine mammary gland homeostasis and human breast cancer still remains under debate. Using in vivo lineage tracing and triple negative breast cancer (TNBC) patient derived xenografts we demonstrate that the repopulating capacity in normal mammary epithelial cells and tumorigenic capacity in TNBC is independent of expression of EMT-associated genes...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29158396/emt-programs-promote-basal-mammary-stem-cell-and-tumor-initiating-cell-stemness-by-inducing-primary-ciliogenesis-and-hedgehog-signaling
#17
Vincent J Guen, Tony E Chavarria, Cornelia Kröger, Xin Ye, Robert A Weinberg, Jacqueline A Lees
Tissue regeneration relies on adult stem cells (SCs) that possess the ability to self-renew and produce differentiating progeny. In an analogous manner, the development of certain carcinomas depends on a small subset of tumor cells, called "tumor-initiating cells" (TICs), with SC-like properties. Mammary SCs (MaSCs) reside in the basal compartment of the mammary epithelium, and their neoplastic counterparts, mammary TICs (MaTICs), are thought to serve as the TICs for the claudin-low subtype of breast cancer...
November 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29156517/mir-504-inhibits-cell-proliferation-and-invasion-by-targeting-loxl2-in-non-small-cell-lung-cancer
#18
Ming-Fan Ye, Ji-Guang Zhang, Tian-Xing Guo, Xiao-Jie Pan
BACKGROUND: MicroRNAs (miRNAs) play crucial roles in tumor initiation and development. The aim of the study was to explore the clinicopathological role and functional effects of miR-504 in non small cell lung cancer (NSCLC). METHODS: Quantitative reverse transcription polymerase chain reaction (QRT-PCR) was applied to detect the expression of miR-504 in 55 cases of NSCLC tissues and matched adjacent normal tissues in NSCLC patients. MTT, colony formation and transwell invasion assays were performed to evaluate the effects of miR-504 on cell proliferation and invasion, respectively...
November 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29152770/cytoplasmic-localization-of-the-cell-polarity-factor-scribble-supports-liver-tumor-formation-and-tumor-cell-invasiveness
#19
Shan Wan, Anne-Sophie Meyer, Sofia Maria Elisabeth Weiler, Christian Rupp, Marcell Tóth, Carsten Sticht, Stephan Singer, Stefan Thomann, Stephanie Roessler, Marina Schorpp-Kistner, Jennifer Schmitt, Norbert Gretz, Peter Angel, Darjus Felix Tschaharganeh, Jens Marquardt, Peter Schirmacher, Federico Pinna, Kai Breuhahn
The loss of epithelial cell polarity plays an important role in the development and progression of liver cancer. However, the specific molecular mechanisms supporting tumor initiation and progression are poorly understood. In this study, transcriptome data and immunofluorescence stains of tissue samples derived from hepatocellular carcinoma (HCC) patients revealed that overexpression associated with cytoplasmic localization of the baso-lateral cell polarity complex protein Scribble (Scrib) correlated with poor prognosis of HCC patients...
November 20, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29152096/the-non-canonical-ubiquitin-activating-enzyme-uba6-suppresses-epithelial-mesenchymal-transition-of-mammary-epithelial-cells
#20
Xianpeng Liu, Limin Sun, Demirkan B Gursel, Chonghui Cheng, Sui Huang, Alfred W Rademaker, Seema A Khan, Jun Yin, Hiroaki Kiyokawa
Ubiquitination plays critical roles in the regulation of oncoproteins and tumor suppressors during carcinogenesis. The two ubiquitin activating enzymes (E1) in human genome, UBA1 and UBA6, initiate ubiquitination by ATP-dependent activation of ubiquitin. Recent evidence suggests that UBA1 and UBA6 play partially overlapped yet distinct roles in controlling the proteome. Here we demonstrate that ubiquitination pathways initiated specifically by UBA6 set a suppressive barrier against critical steps of mammary carcinogenesis such as loss of polarity, anoikis resistance and epithelial-mesenchymal transition (EMT)...
October 20, 2017: Oncotarget
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