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colon cancer, EMT

Nefeli Zacharopoulou, Anna Tsapara, Galatea Kallergi, Evi Schmid, Saad Alkahtani, Saud Alarifi, Philip N Tsichlis, Sotirios C Kampranis, Christos Stournaras
BACKGROUND/AIMS: The epigenetic factor KDM2B is a histone demethylase expressed in various tumors. Recently, we have shown that KDM2B regulates actin cytoskeleton organization, small Rho GTPases signaling, cell-cell adhesion and migration of prostate tumor cells. In the present study, we addressed its role in regulating EMT and small GTPases expression in colon tumor cells. METHODS: We used RT-PCR for the transcriptional analysis of various genes, Western blotting for the assessment of protein expression and immunofluorescence microscopy for visualization of fluorescently labeled proteins...
May 14, 2018: Cellular Physiology and Biochemistry
Hong Shen, Ling Yin, Ganlu Deng, Cao Guo, Ying Han, Yiyi Li, Changjing Cai, Yaojie Fu, Shanshan Liu, Shan Zeng
Activation of autophagy significantly affects cancer cell behaviors, such as proliferation, differentiation, and invasiveness. Epithelial-to-mesenchymal transition (EMT) as an initial step of malignant transformation of cancer cells was linked to the activation of autophagy, but the detailed molecular mechanisms are still unknown. The present study investigates the effects of Beclin-1, a key molecule involved in activation of autophagy, on EMT of colon cancer cells. The normal colon epithelia cell line of CCD-18Co and six colon cancer cell lines with different expression levels of Beclin-1 were used in this study...
May 8, 2018: Journal of Cellular Biochemistry
Kari Trumpi, Nicola Frenkel, Timo Peters, Nicoline M Korthagen, Jennifer M J Jongen, Daniëlle Raats, Helma van Grevenstein, Yara Backes, Leon M Moons, Miangela M Lacle, Jan Koster, Danny Zwijnenburg, Inne H M Borel Rinkes, Onno Kranenburg
Primary human colorectal tumors with a high stromal content have an increased capacity to metastasize. Cancer-associated fibroblasts (CAFs) promote metastasis, but the contribution of other stromal cell types is unclear. Here we searched for additional stromal cell types that contribute to aggressive tumor cell behavior. By making use of the 'immunome compendium'-a collection of gene signatures reflecting the presence of specific immune cell-types-we show that macrophage signatures are most strongly associated with a high CAF content and with poor prognosis in multiple large cohorts of primary tumors and liver metastases...
April 13, 2018: Oncotarget
Yuanfei Li, Guoqiang Zhu, Huihong Zhai, Junmei Jia, Wenhui Yang, Xiaoqing Li, Lixin Liu
Epithelial-mesenchymal transition (EMT) is critical in the progression of numerous types of carcinoma, and endows invasive and metastatic properties upon cancer cells. The tumor microenvironment facilitates tumor metastasis to distant organs. Various signaling pathways contribute to this process. In the present study, SW480 colon adenocarcinoma cells were treated with transforming growth factor-β1 (TGF-β1; 10 ng/ml) and tumor necrosis factor-α (TNF-α; 20 ng/ml), alone or in combination, for 72 h, and EMT was assessed using immunofluorescence, western blot analysis and migration assays...
May 2018: Oncology Letters
Siming Yu, Linnan Li, Wei Tian, Dan Nie, Wei Mu, Fang Qiu, Yu Liu, Xinghan Liu, Xiaofeng Wang, Zhimin Du, Wen-Feng Chu, Baofeng Yang
BACKGROUND AND PURPOSE: This study aimed to verify the antitumour effects of PEP06, a polypeptide modified from endostatin, and to elaborate the mechanisms in treating colorectal carcinoma (CRC). EXPERIMENTAL APPROACH: After PEP06 treatment, cell proliferation and migration assays were performed in CRC cells. Epithelial mesenchymal transition (EMT) progression was determined with Western blot, immunofluorescent staining and immunohistochemistry in vitro and in a residual xenograft model...
May 3, 2018: British Journal of Pharmacology
Hanqing Hu, Meng Wang, Hongwei Wang, Zheng Liu, Xu Guan, Runkun Yang, Rui Huang, Qingchao Tang, Chaoxia Zou, Guiyu Wang, Xu Gao, Xishan Wang
BACKGROUND/AIMS: Colorectal cancer (CRC) is a malignancy that has high morbidity and mortality and is initiated from accumulative genetic events. Although much effort has been made to elucidate the genetic mechanism underlying this disease, it still remains unknown. Here, we discovered a novel role for multiple epidermal growth factor-like domains protein 6 (MEGF6) in CRC, namely, that it induces the epithelial-to-mesenchymal transition (EMT) to promote CRC metastasis via the transforming growth factor beta (TGFβ)/SMAD signaling pathway...
April 26, 2018: Cellular Physiology and Biochemistry
Kyoung Ah Kang, Yea Seong Ryu, Mei Jing Piao, Kristina Shilnikova, Hee Kyoung Kang, Joo Mi Yi, Mathias Boulanger, Rosa Paolillo, Guillaume Bossis, Sung Young Yoon, Seong Bong Kim, Jin Won Hyun
The therapeutic benefits offered by 5-fluorouracil (5-FU) are limited because of the acquisition of drug resistance, the main cause of treatment failure and metastasis. The ability of the cancer cells to undergo epithelial-mesenchymal transition (EMT) contributes significantly to cancer metastatic potential and chemo-resistance. However, the underlying molecular mechanisms of 5-FU-resistance have remained elusive. Here, we show that reactive oxygen species (ROS), produced by dual oxidase 2 (DUOX2), promote 5-FU-induced EMT...
April 23, 2018: Redox Biology
Mintu Pal, Sourya Bhattacharya, Gazal Kalyan, Saugata Hazra
The major hallmarks of Epithelial-Mesenchymal Transition (EMT) is the loss of epithelial cell polarity and loss of expression of the cell- cell adhesion molecule like E-cadherin and acquired mesenchymal cells marker called N-Cadherin. This phenotypical changes of E-M plasticity of cells is extensively considered to be a crucial factor for tumor cells invasion and cancer metastasis; landmark events for transforming a locally growing tumor (benign tumor) into a systemic and live-threatening disease (malignant tumor)...
April 16, 2018: Experimental Cell Research
Kecheng Wang, Meng Zhang, Cong Wang, Xiaofei Ning
Increasing evidences have demonstrated that aberrant expressions of long non-coding RNAs (lncRNAs) are closely correlated to various malignancies, as well as colon carcinoma (CC). The aim of this study was to investigate the role of lncRNA long intergenic noncoding RNA 001296 (LINC01296) in tumorigenesis of CC. The result of the quantitative real-time polymerase chain reaction (qRT-PCR) demonstrated that LINC01296 was upregulated in CC cancerous tissues and cell lines compared to adjacent normal tissue and normal liver cell lines...
April 19, 2018: Oncology Research
Teresa P Raposo, Mireia Sueca Comes, Adeyemi Idowu, Bora Agit, James Hassall, Wakkas Fadhil, Robert Nica, Rupert Ecker, Takashi Yao, Mohammad Ilyas
INTRODUCTION: CD10 is a cell membrane-bound endopeptidase which is expressed in normal small bowel but not in normal colon. It is aberrantly expressed in a small proportion of colorectal cancers (CRC) and this has been associated with liver metastasis and poor prognosis. We sought to investigate the mechanism of CD10 activity and its association with clinicopathological features. MATERIAL AND METHODS: CD10 was stably knocked down by lentiviral shRNA transduction in the CRC cell lines SW480 and SW620 which are derived from a primary tumour and its corresponding metastasis respectively...
April 11, 2018: Experimental and Molecular Pathology
Sadia Afrin, Francesca Giampieri, Massimiliano Gasparrini, Tamara Y Forbes-Hernández, Danila Cianciosi, Patricia Reboredo-Rodriguez, Piera Pia Manna, Jiaojiao Zhang, Josè L Quiles, Maurizio Battino
Despite its high content of phenolic compounds, the chemopreventive activity of Manuka honey (MH) is still elusive. The aim of the present work was to evaluate the effects of MH on oxidative stress, antioxidant enzymes, cellular metabolism and the metastatic ability in HCT-116 and LoVo cells, paying particular attention to the molecular mechanisms involved. We observed a strong induction of oxidative stress after MH treatment since it augmented the accumulation of reactive oxygen species and increased the damage to proteins, lipids and DNA...
April 12, 2018: Food & Function
Kaiming Wu, Kaiwu Xu, Kuanzhi Liu, Jiehong Huang, Jianhui Chen, Jian Zhang, Ning Zhang
Colon cancer is the third most commonly diagnosed and deadly cancer worldwide. Efforts have been made to characterize its pathological mechanisms and to explore new therapeutic targets of this disease. Aberrant expression of long noncoding RNAs (lncRNAs) has been associated with the pathogenesis of colon cancer. In the current study, we aimed to define the biological mechanism of the lncRNA BC200 in colon cancer. Here, we found that expression of BC200 was up-regulated in colon cancer tissues as compared with adjacent non-cancerous tissues...
April 3, 2018: International Journal of Biochemistry & Cell Biology
Andy Chen, Luqi Wang, Shengzhi Liu, Yue Wang, Yunlong Liu, Mu Wang, Harikrishna Nakshatri, Bai-Yan Li, Hiroki Yokota
Bone is a frequent site of metastasis from breast cancer. To understand the potential role of osteocytes in bone metastasis, we investigated tumor-osteocyte interactions using two cell lines derived from the MDA-MB-231 breast cancer cells, primary breast cancer cells, and MLO-A5/MLO-Y4 osteocyte cells. When three-dimensional (3D) tumor spheroids were grown with osteocyte spheroids, tumor spheroids fused with osteocyte spheroids and shrank. This size reduction was also observed when tumor spheroids were exposed to conditioned medium isolated from osteocyte cells...
April 3, 2018: Scientific Reports
Ben Yue, Chenchen Liu, Huimin Sun, Mengru Liu, Chenlong Song, Ran Cui, Shenglong Qiu, Ming Zhong
We previously demonstrated that long non-coding RNA cytoskeleton regulator RNA (CYTOR), also known as Linc00152, was significantly overexpressed in colon cancer and conferred resistance to oxaliplatin-induced apoptosis. At the same time, elevated CYTOR expression was also reported in gastric cancer and exerted influences on epithelial-mesenchymal transition (EMT) markers. However, the precise mechanism by which CYTOR promotes the EMT phenotype and cancer metastasis remains poorly understood. Here, we showed that loss of epithelial characteristics and simultaneous gain of mesenchymal features correlated with CYTOR expression...
March 6, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Min Zhou, Xinjian Liu, Zonghai Li, Qian Huang, Fang Li, Chuan-Yuan Li
Caspase-3 (CASP3) is a major mediator of apoptosis activated during cellular exposure to cytotoxic drugs, radiotherapy or immunotherapy. It is often used as a marker for efficacy of cancer therapy. However, recent reports indicate that caspase-3 has also non-apoptotic roles such as promotion of tumor relapse and tumor angiogenesis. Therefore, the roles of caspase-3 in tumor progression remain to be defined clearly. In our study, we established caspase-3 knockout (KO) colon cancer cell lines by use of the CRISPR technology...
March 10, 2018: International Journal of Cancer. Journal International du Cancer
Dimitrios Tsoumas, Sofia Nikou, Efstathia Giannopoulou, Spyridon Champeris Tsaniras, Chaido Sirinian, Ioannis Maroulis, Stavros Taraviras, Vassiliki Zolota, Haralabos P Kalofonos, Vasiliki Bravou
BACKGROUND/AIM: Epithelial-mesenchymal transition (EMT) and cancer stem cells (CSC) are critically implicated in cancer metastasis and chemoresistance. Herein, we investigated integrin-linked kinase (ILK)'s role in human colon cancer (CRC) progression and chemoresistance in relation to EMT and CSC markers. PATIENTS AND METHODS: Expression of ILK, EMT and CSC markers were evaluated by immunohistochemistry in 149 CRC samples. We also generated colon cancer cells resistant to 5-FU and oxaliplatin and studied the effect of ILK inhibition on drug response by MTT assay and on EMT and CSC markers' expression...
March 2018: Cancer Genomics & Proteomics
Nicolas Aznar, Jason Ear, Ying Dunkel, Nina Sun, Kendall Satterfield, Fang He, Nicholas A Kalogriopoulos, Inmaculada Lopez-Sanchez, Majid Ghassemian, Debashis Sahoo, Irina Kufareva, Pradipta Ghosh
Cellular proliferation, differentiation, and morphogenesis are shaped by multiple signaling cascades, and their dysregulation plays an integral role in cancer progression. Three cascades that contribute to oncogenic potential are those mediated by Wnt proteins and the receptor Frizzled (FZD), growth factor receptor tyrosine kinases (RTKs), and heterotrimeric G proteins and associated GPCRs. Daple is a guanine nucleotide exchange factor (GEF) for the G protein Gαi Daple also binds to FZD and the Wnt/FZD mediator Dishevelled (Dvl), and it enhances β-catenin-independent Wnt signaling in response to Wnt5a-FZD7 signaling...
February 27, 2018: Science Signaling
Dongdong Sun, Weixing Shen, Feng Zhang, Huisen Fan, Changliang Xu, Liu Li, Jiani Tan, Yunjie Miao, Haibin Zhang, Ye Yang, Haibo Cheng
Colon cancer is the third most frequently diagnosed malignancy and has high morbidity worldwide. Epithelial-mesenchymal transition (EMT) has been increasingly implicated in colon cancer progression and metastasis. The present study was aimed to evaluate the potential antitumor activity of α-hederin, a monodesmosidic triterpenoid saponin isolated from Hedera helix, in human SW620 colon cancer cells stimulated with interleukin 6 (IL-6) for mimicking the tumor inflammatory microenvironment in vivo. Cell viability assay showed that IL-6 at 6...
May 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Yun Zhu, Cindy Wang, Scott A Becker, Katie Hurst, Lourdes M Nogueira, Victoria J Findlay, E Ramsay Camp
Epithelial-to-mesenchymal transition (EMT) has been closely linked with therapy resistance and cancer stem cells (CSCs). However, EMT pathways have proven challenging to therapeutically target. MicroRNA 145 (miR-145) targets multiple stem cell transcription factors and its expression is inversely correlated with EMT. Therefore, we hypothesized that miR-145 represents a therapeutic target to reverse snail family transcriptional repressor 1 (SNAI1)-mediated stemness and radiation resistance (RT). Stable expression of SNAI1 in DLD1 and HCT116 cells (DLD1-SNAI1; HCT116-SNAI1) increased expression of Nanog and decreased miR-145 expression compared to control cells...
March 7, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Yoko Fujii-Nishimura, Ken Yamazaki, Yohei Masugi, Junya Douguchi, Yutaka Kurebayashi, Naoto Kubota, Hidenori Ojima, Minoru Kitago, Masahiro Shinoda, Akinori Hashiguchi, Michiie Sakamoto
Epithelial-mesenchymal transition (EMT) promotes invasion and metastasis of pancreatic ductal adenocarcinoma (PDAC). However, the importance of its reverse process, mesenchymal-epithelial transition (MET), for PDAC remains unclear. We aimed to characterize the histological finding "focal differentiation" in PDAC at perineural invasion sites in the context of MET and to investigate the role of Schwann cells in inducing tumor MET. Tumor differentiation and immunohistochemical expressions of E-cadherin, SMAD3, and vimentin at perineural invasion sites were examined in 168 PDAC tissues...
April 2018: Pathology International
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