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https://www.readbyqxmd.com/read/28319088/reference-component-analysis-of-single-cell-transcriptomes-elucidates-cellular-heterogeneity-in-human-colorectal-tumors
#1
Huipeng Li, Elise T Courtois, Debarka Sengupta, Yuliana Tan, Kok Hao Chen, Jolene Jie Lin Goh, Say Li Kong, Clarinda Chua, Lim Kiat Hon, Wah Siew Tan, Mark Wong, Paul Jongjoon Choi, Lawrence J K Wee, Axel M Hillmer, Iain Beehuat Tan, Paul Robson, Shyam Prabhakar
Intratumoral heterogeneity is a major obstacle to cancer treatment and a significant confounding factor in bulk-tumor profiling. We performed an unbiased analysis of transcriptional heterogeneity in colorectal tumors and their microenvironments using single-cell RNA-seq from 11 primary colorectal tumors and matched normal mucosa. To robustly cluster single-cell transcriptomes, we developed reference component analysis (RCA), an algorithm that substantially improves clustering accuracy. Using RCA, we identified two distinct subtypes of cancer-associated fibroblasts (CAFs)...
March 20, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28319071/xrn2-promotes-emt-and-metastasis-through-regulating-maturation-of-mir-10a
#2
H Zhang, Y Lu, E Chen, X Li, B Lv, H G Vikis, P Liu
MicroRNAs (miRNAs) have been proposed as critical regulatory molecules in the epithelial-mesenchymal transition (EMT) program. However, the roles of mature miRNA biogenesis during EMT process needs to be defined. Here we determined that increased expression of XRN2 induced EMT and promoted metastasis in vitro and in vivo. Furthermore, we uncovered that XRN2 functions as pro-metastatic gene, which accelerates miR-10a maturation by binding pre-miR-10a in a DICER-independent manner. These findings suggest that XRN2 is a novel regulator of EMT that contributes to the metastatic processes in lung cancer through a novel miRNA regulatory mechanism...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28318921/influence-of-tgf-%C3%AE-1-on-tumor-transition-in-oral-cancer-cell-and-bmsc-co-cultures
#3
F Böhrnsen, F Godek, J Kiesel, F J Kramer, P Brockmeyer, H Schliephake
OBJECTIVES: TGF-β1 signaling modulates epithelial mesenchymal transitions (EMT) of head and neck squamous cell carcinoma (HNSCC). Bone marrow mesenchymal stromal cells (BMSC) are able to exert a regulating influence on the expression of markers of EMT in HNSCC cells. It was thus the aim of this study to test the hypothesis that TGF-β1 modulates the interactions of tumor transition between BMSCs and HNSCC, affecting the expression of E-cadherin, Vimentin, Snail, Twist, MMP14 and beta-catenin...
February 17, 2017: Journal of Cranio-maxillo-facial Surgery
https://www.readbyqxmd.com/read/28317368/mir-186-inhibited-migration-of-nsclc-via-targeting-cdc42-and-effecting-emt-process
#4
Ying Dong, Xintian Jin, Zhiqiang Sun, Yueming Zhao, Xianjing Song
In this study, qRT-PCR was employed to identify that miR-186 expression level in NSCLC tissues are highly associated with lymph node metastasis. In addition, through the application of western blotting, luciferase assay and qRT-PCR, it was found that miR-186 targeted 3'UTR of cdc42 mRNA and down-regulated cdc42 protein level in a post-transcriptional manner. Transwell assay indicated that cdc42 partially reversed the effect of miR-186 mimics. Besides, miR-186 was proved to regulate EMT by influencing biomarkers of this process and cell adhesion ability...
March 20, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28316213/-expression-of-lim-and-sh3-protein-1-in-renal-clear-cell-carcinoma-and-its-effects-on-invasion-and-migration-of-renal-clear-cell-carcinoma-786-o-cells
#5
B Jin, L Gao, W Li, J C Chen, R M Wen, J Q Wang
Objective: To investigate the expression of LIM and SH3 protein 1 (LASP1) in renal cell carcinoma and its significance in the invasion and migration of renal clear cell carcinoma 786-O cell line. Methods: The expression level of LASP1 in 41 cases of renal cell carcinoma tissues and normal renal tissues was analyzed by immunohistochemistry. The relationship between the expression level of LASP1 and clinical characteristics was further analyzed. Expression of LASP1 in 10 cases of tumor tissues with or without lymph node metastasis was analyzed by Western blot...
March 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28316062/cldn-1-promoted-the-epithelial-to-migration-and-mesenchymal-transition-emt-in-human-bronchial-epithelial-cells-via-notch-pathway
#6
Jing Lv, Baohua Sun, Zhitao Mai, Mingming Jiang, Junfeng Du
Claudin-1 (CLDN-1) is one of main tight junction components that play an important role in epithelial-mesenchymal transition (EMT). However, the effects of CLDN-1 on the migration and EMT induced by TGF-β1 in primary normal human bronchial epithelial (NHBE) and BEAS-2B cells have not been clear. The expression of CLDN-1 was quantified by Western blotting in NHBE and BEAS-2B cells. Cell migration and invasion were detected using transwell assays. The expression level of E-cadherin, N-cadherin, α-SMA, and Vimentin was evaluated by quantitative real-time PCR and Western blotting...
March 18, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28315789/involvement-of-epithelial-mesenchymal-transition-afforded-by-activation-of-lox-1-tgf-%C3%AE-1-klf6-signaling-pathway-in-diabetic-pulmonary-fibrosis
#7
Xiao-Zhou Zou, Zhi-Cheng Gong, Ting Liu, Fang He, Tian-Tian Zhu, Dai Li, Wei-Fang Zhang, Jun-Lin Jiang, Chang-Ping Hu
BACKGROUND AND OBJECTIVE: Diabetic pulmonary fibrosis is a severe disease that increases mortality risk of diabetes. However, the molecular mechanisms leading to pulmonary fibrosis in diabetes are poorly understood. This study investigated the roles of epithelial-mesenchymal transition (EMT) and the associated molecular mechanisms in streptozotocin (STZ)-induced rat pulmonary fibrosis. METHODS: The rat model of diabetic pulmonary fibrosis was established by intraperitoneal injection of a single dose of STZ (35 mg/kg)...
March 15, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28315783/role-of-protein-glycosylation-in-cancer-metastasis
#8
REVIEW
Leticia Oliveira-Ferrer, Karen Legler, Karin Milde-Langosch
Although altered glycosylation has been detected in human cancer cells decades ago, only investigations in the last years have enormously increased our knowledge about the details of protein glycosylation and its role in tumour progression. Many proteins, which are heavily glycosylated, i.e. adhesion proteins or proteases, play an important role in cancer metastasis that represents the crucial and frequently life-threatening step in progression of most tumour types. Compared to normal tissue, tumour cells often show altered glycosylation patters with appearance of new tumour-specific antigens...
March 15, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28315692/role-of-epithelial-mesenchymal-transition-emt-and-fibroblast-function-in-cerium-oxide-nanoparticles-induced-lung-fibrosis
#9
Jane Ma, Bridget Bishoff, R R Mercer, Mark Barger, Diane Schwegler-Berry, Vincent Castranova
The emission of cerium oxide nanoparticles (CeO2) from diesel engines, using cerium compounds as a catalyst to lower the diesel exhaust particles, is a health concern. We have previously shown that CeO2 induced pulmonary inflammation and lung fibrosis. The objective of the present study was to investigate the modification of fibroblast function and the role of epithelial-mesenchymal transition (EMT) in CeO2-induced fibrosis. Male Sprague-Dawley rats were exposed to CeO2 (0.15 to 7mg/kg) by a single intratracheal instillation and sacrificed at various times post-exposure...
March 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28315433/increased-semaphorin-3c-expression-promotes-tumor-growth-and-metastasis-in-pancreatic-ductal-adenocarcinoma-by-activating-the-erk1-2-signaling-pathway
#10
Xuejun Xu, Zhiping Zhao, Sixiang Guo, Jian Li, Songsong Liu, Yu You, Bing Ni, Huaizhi Wang, Ping Bie
Pancreatic cancer is characterized by neural alterations and aberrant expression of neural-specific factors. Semaphorins have been recognized as key contributors in axon guidance, the immune response and tumor progression. Recent studies have suggested the involvement of Semaphorin 3c (sema3c) in tumorigenesis and metastasis in numerous types of cancer, however, the clinical significance of sema3c and its role in the growth and metastasis of pancreatic ductal adenocarcinoma (PDAC) remain unclear. In this study, we found that aberrant sema3c expression was positively associated with a particular tumor stage and correlated with poor survival of PDAC patients...
March 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28315334/bapx1-mediates-transforming-growth-factor-%C3%AE-induced-epithelial-mesenchymal-transition-and-promotes-a-malignancy-phenotype-of-gastric-cancer-cells
#11
Shi Ouyang, Guodong Zhu, Lei Ouyang, Yuhao Luo, Rui Zhou, Changqie Pan, Jianping Bin, Yulin Liao, Wangjun Liao
The homeoprotein Bapx1 is an important regulator of gastroduodenal tract morphogenesis. Here, we investigated how Bapx1 influences gastric cancer (GC) prognosis and elucidated the underlying mechanisms. Bapx1 expression was greater in GC tissues compared to adjacent non-tumor tissues and expression was positively correlated with mortality, lymph node and distance metastasis. Silencing Bapx1 diminished cell invasion/migration and decreased mesenchymal phenotypes. Transforming growth factor-β (TGF-β) induced Bapx1 expression and epithelial-mesenchymal transition (EMT) in GC cells...
March 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28315203/adc-histogram-analysis-of-cervical-cancer-aids-detecting-lymphatic-metastases-a-preliminary-study
#12
Stefan Schob, Hans Jonas Meyer, Nikolaos Pazaitis, Dominik Schramm, Kristina Bremicker, Marc Exner, Anne Kathrin Höhn, Nikita Garnov, Alexey Surov
PURPOSE: Apparent diffusion coefficient (ADC) histogram analysis has been used to some extent in cervical cancer (CC) to distinguish between low-grade and high-grade tumors. Although this differentiation is undoubtedly helpful, it would be even more crucial in the presurgical setting to determine whether a tumor already gained the potential to metastasize via the lymphatic system. So far, no studies investigated the potential of 3T ADC histogram analysis in CC to differentiate between nodal-positive and nodal-negative entities...
March 17, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28314278/elevated-preoperative-serum-cea-level-is-associated-with-poor-prognosis-in-patients-with-hepatocellular-carcinoma-through-the-epithelial-mesenchymal-transition
#13
Masato Yoshikawa, Yuji Morine, Tetsuya Ikemoto, Satoru Imura, Jun Higashijima, Shuichi Iwahashi, Y U Saito, Chie Takasu, Shinichiro Yamada, Daichi Ishikawa, Hiroki Teraoku, Atsushi Takata, Toshiaki Yoshimoto, Mitsuo Shimada
BACKGROUND: Serum carcinoembryonic antigen (CEA) is used as an indicator of tumor progression in a variety of carcinomas. A subset of patients with hepatocellular carcinoma (HCC) exhibit increased serum CEA level, but the significance of this is unclear. In this study, we investigated the prognosis of patients with HCC with increased serum CEA, and explored the correlations with expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and epithelial-mesenchymal transition (EMT) and tumor angiogenesis...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28314256/hydrogen-peroxide-enhances-tgf%C3%AE-mediated-epithelial-to-mesenchymal-transition-in-human-mammary-epithelial-mcf-10a-cells
#14
Daisuke Iizuka, Megumi Sasatani, Mary Helen Barcellos-Hoff, Kenji Kamiya
AIM: This study investigated the effect of reactive oxygen species (ROS) on transforming growth factor (TGF)-β-mediated epithelial-to-mesenchymal transition (EMT) in order to clarify the influence of ROS and TGFβ on the induction of dysplasia and ultimately, tumorigenesis. MATERIALS AND METHODS: Confluent MCF-10A human mammary epithelial cells were treated with H2O2 for 1 h, then reseeded at low density in the presence of TGFβ and cultured until confluence. RESULTS: Hydrogen peroxide (H2O2, 250 μM) enhanced TGFβ-mediated EMT, as evidenced by increased expression of EMT-associated transcription factors, which was accompanied by increased nuclear localization of phosphorylated SMAD family member 2 (SMAD2) and up-regulation of the TGFβ signaling pathway components mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28303918/effects-of-matrix-stiffness-on-epithelial-to-mesenchymal-transition-like-processes-of-endometrial-epithelial-cells-implications-for-the-pathogenesis-of-endometriosis
#15
Sachiko Matsuzaki, Claude Darcha, Jean-Luc Pouly, Michel Canis
Endometriosis is defined as the presence of endometrial glands and stroma within extrauterine sites. Our previous study revealed an epithelial to mesenchymal transition (EMT)-like process in red peritoneal endometriosis, whereas membrane localization of E-cadherin was well maintained in epithelial cells of deep infiltrating endometriosis (DIE). Here we show that endometrial epithelial cells (EEE) grown on polyacrylamide gel substrates (PGS) of 2 kilopascal (kPa), a soft matrix, initiate a partial EMT-like process with transforming growth factor-β1 (TGF-β1) stimulation...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28302721/involvement-of-notch1-signaling-in-malignant-progression-of-a549-cells-subjected-to-prolonged-cadmium-exposure
#16
Kota Fujiki, Hisako Inamura, Takamitsu Miyayama, Masato Matsuoka
Cadmium exposure is known to increase lung cancer risk, but the underlying molecular mechanisms in cadmium-stimulated progression of malignancy are unclear. Here, we examined the effects of prolonged cadmium exposure on the malignant progression of A549 human lung adenocarcinoma cells and the roles of Notch1, hypoxia-inducible factor 1α (HIF-α), and insulin-like growth factor 1 receptor (IGF-1R)/Akt/extracellular signal-regulated kinase (ERK)/p70 S6 kinase 1 (S6K1) signaling pathways. Exposing A549 cells to 10 or 20 μM cadmium chloride (CdCl2) for 9-15 weeks induced a high proliferative potential, the epithelial-mesenchymal transition (EMT), stress fiber formation, high cell motility, and resistance to anti-tumor drugs...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28302417/muc1-c-oncoprotein-integrates-a-program-of-emt-epigenetic-reprogramming-and-immune-evasion-in-human-carcinomas
#17
REVIEW
Hasan Rajabi, Donald Kufe
The MUC1 gene evolved in mammalian species to provide protection of epithelia. The transmembrane MUC1 C-terminal subunit (MUC1-C) signals stress to the interior of the epithelial cell and, when overexpressed as in most carcinomas, functions as an oncoprotein. MUC1-C induces the epithelial-mesenchymal transition (EMT) by activating the inflammatory NF-κB p65 pathway and, in turn, the EMT-transcriptional repressor ZEB1. Emerging evidence has indicated that MUC1-C drives a program integrating the induction of EMT with activation of stem cell traits, epigenetic reprogramming and immune evasion...
March 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28301605/ocf-can-repress-tumor-metastasis-by-inhibiting-epithelial-mesenchymal-transition-involved-in-pten-pi3k-akt-pathway-in-lung-cancer-cells
#18
Ye Yang, Shuang Qiu, Lei Qian, Yuan Tian, Yingna Chen, Lei Bi, Weiping Chen
A component formula with definite compositions provides a new approach to treat various diseases. Salvia miltiorrhiza and Panax ginseng are widely used in China because of their antitumor properties. In the previous study, the optimizing component formula (OCF), prepared with salvianolic acids, ginsenosides, and ginseng polysaccharides (5, 10, and 5 mg·L-1, respectively) extracted from S. miltiorrhiza and P. ginseng on the basis of IC50 in lung cancer A549 cells and damage minimization on human bronchial epithelial cells in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28300833/pi3k-akt-mediated-upregulation-of-wdr5-promotes-colorectal-cancer-metastasis-by-directly-targeting-znf407
#19
Xin Tan, Shuai Chen, Jiangxue Wu, Jiaxin Lin, Changchuan Pan, Xiaofang Ying, Zhizhong Pan, Lin Qiu, Ranyi Liu, Rong Geng, Wenlin Huang
Colorectal cancer (CRC) is the third most common cause of cancer deaths, and has a high rate of liver and lung metastasis. Unfortunately, distant metastasis is the main barrier for advanced CRC therapy and leads to a very low survival rate. In this study, we identified WDR5, a vital factor that regulates vertebrate development and cell self-renewal and reprogramming, as a novel prognostic marker and therapeutic target for CRC patients. We demonstrate that WDR5 is upregulated in CRC tissues and promotes CRC metastasis both in vitro and in vivo...
March 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28299802/bmp-and-notch-interaction-in-crc-subtypes
#20
Shazia Irshad, Mukesh Bansal, Paolo Guarnieri, Hayley Davis, Ayman Al Haj Zen, Brygida Baran, Claudia Maria Assunta Pinna, Haseeb Rahman, Sujata Biswas, Chiara Bardella, Rosemary Jeffery, Lai Mun Wang, James Edward East, Annabelle Lewis, Ian Tomlinson, Simon John Leedham
The functional role of Bone Morphogenetic Protein (BMP) signalling in colorectal cancer (CRC) is poorly defined, with contradictory results in cancer cell line models reflecting the inherent difficulties of assessing a signalling pathway that is context dependent and subject to genetic constraints. By assessing the transcriptional response of a diploid human colonic epithelial cell line to BMP ligand stimulation we generated a prognostic BMP signalling signature, which was applied to multiple CRC datasets to investigate BMP heterogeneity across CRC molecular subtypes...
March 15, 2017: Journal of Pathology
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