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https://www.readbyqxmd.com/read/28431931/peroxiredoxin-5-promotes-the-epithelial-mesenchymal-transition-in-colon-cancer
#1
Hye-Mi Ahn, Jin-Woo Yoo, Seunghoon Lee, Hong Jun Lee, Hyun-Shik Lee, Dong-Seok Lee
Globally, colorectal cancer (CRC) is common cause of cancer-related deaths. The high mortality rate of patients with colon cancer is due to cancer cell invasion and metastasis. Initiation of the epithelial-to-mesenchymal transition (EMT) is essential for the tumorigenesis. Peroxiredoinxs (PRX1-6) have been reported to be overexpressed in various tumor tissues, and involved to be responsible for tumor progression. However, the exact role of PRX5 in colon cancer remains to be investigated enhancing proliferation and promoting EMT properties...
April 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28431272/specific-microrna-mrna-regulatory-network-of-colon-cancer-invasion-mediated-by-tissue-kallikrein-related-peptidase-6
#2
Earlphia Sells, Ritu Pandey, Hwudaurw Chen, Bethany A Skovan, Haiyan Cui, Natalia A Ignatenko
Metastatic colon cancer is a major cause of deaths among colorectal cancer (CRC) patients. Elevated expression of kallikrein 6 (KLK6), a member of a kallikrein subfamily of peptidase S1 family serine proteases, has been reported in CRC and is associated with low patient survival rates and poor disease prognosis. We knocked down KLK6 expression in HCT116 colon cancer cells to determine the significance of KLK6 expression for metastatic dissemination and to identify the KLK6-associated microRNAs (miRNAs) signaling networks in metastatic colon cancer...
April 18, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28418862/niclosamide-is-a-potential-therapeutic-for-familial-adenomatosis-polyposis-by-disrupting-axin-gsk3-interaction
#3
Sung Yong Ahn, Nam Hee Kim, Kyungro Lee, Yong Hoon Cha, Ji Hye Yang, So Young Cha, Eunae Sandra Cho, Yoonmi Lee, Jeong Seok Cha, Hyun Soo Cho, Yoon Jeon, Young-Su Yuk, Suebean Cho, Kyoung Tai No, Hyun Sil Kim, Ho Lee, Jiwon Choi, Jong In Yook
The epithelial-mesenchymal transition (EMT) is implicated in tumorigenesis and cancer progression, and canonical Wnt signaling tightly controls Snail, a key transcriptional repressor of EMT. While the suppression of canonical Wnt signaling and EMT comprises an attractive therapeutic strategy, molecular targets for small molecules reverting Wnt and EMT have not been widely studied. Meanwhile, the anti-helminthic niclosamide has been identified as a potent inhibitor of many oncogenic signaling pathways although its molecular targets have not yet been clearly identified...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416823/-identification-of-a-new-pro-invasion-factor-in-tumor-microenvironment-progress-in-function-and-mechanism-of-extracellular-atp
#4
W G Fang, X X Tian
Up to 90% of all cancer related morbidity and mortality can be attributed to metastasis. In recent years the study of tumor microenvironment, its cellular and molecular components, and how they can affect neoplastic progression toward metastasis, has become a hot focus in cancer research. Accumulated evidence shows that the formation of metastasis is a multi-step sequential process, in which, the tumor cells continuously interact with the host microenvironment. Host derived factors, i.e. growth factors/inhibitors, angiogenic factors, chemokines, etc...
April 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28414315/the-emt-activator-zeb1-is-a-key-factor-for-cell-plasticity-and-promotes-metastasis-in-pancreatic-cancer
#5
Angela M Krebs, Julia Mitschke, María Lasierra Losada, Otto Schmalhofer, Melanie Boerries, Hauke Busch, Martin Boettcher, Dimitrios Mougiakakos, Wilfried Reichardt, Peter Bronsert, Valerie G Brunton, Christian Pilarsky, Thomas H Winkler, Simone Brabletz, Marc P Stemmler, Thomas Brabletz
Metastasis is the major cause of cancer-associated death. Partial activation of the epithelial-to-mesenchymal transition program (partial EMT) was considered a major driver of tumour progression from initiation to metastasis. However, the role of EMT in promoting metastasis has recently been challenged, in particular concerning effects of the Snail and Twist EMT transcription factors (EMT-TFs) in pancreatic cancer. In contrast, we show here that in the same pancreatic cancer model, driven by Pdx1-cre-mediated activation of mutant Kras and p53 (KPC model), the EMT-TF Zeb1 is a key factor for the formation of precursor lesions, invasion and notably metastasis...
April 17, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28407379/epithelial-mesenchymal-plasticity-and-circulating-tumor-cells-travel-companions-to-metastases
#6
REVIEW
Marie-Emilie Francart, Justine Lambert, Aline M Vanwynsberghe, Erik W Thompson, Morgane Bourcy, Myriam Polette, Christine Gilles
Epithelial-Mesenchymal Transitions (EMT) associated with metastatic progression may contribute to the generation of hybrid phenotypes capable of plasticity. This cellular plasticity would provide tumor cells with an increased potential to adapt to the different microenvironments encountered during metastatic spread. Understanding how EMT may functionally equip Circulating Tumor Cells (CTCs) with an enhanced competence to survive in the blood stream and niche in the colonized organs has thus become a major cancer research axis...
April 13, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28394318/the-evolving-concept-of-cancer-stem-like-cells-in-thyroid-cancer-and-other-solid-tumors
#7
Heather Hardin, Ranran Zhang, Holly Helein, Darya Buehler, Zhenying Guo, Ricardo V Lloyd
The cancer stem-like cell (CSC) hypothesis postulates that a small population of cells in a cancer has self-renewal and clonal tumor initiation properties. These cells are responsible for tumor initiation, growth, recurrence and for resistance to chemotherapy and radiation therapy. CSCs can be characterized using markers such as SSEA-1, SSEA-4, CD44, CD24, ALDEFLUOR and others. CSCs form spheres when they are cultured in serum-free condition in low attachment plates and can generate tumors when injected into immune-deficient mice...
April 10, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28370249/possible-role-of-nuclear-%C3%AE-catenin-in-resistance-to-preoperative-chemoradiotherapy-in-locally-advanced-rectal-cancer
#8
Hiroyuki Takahashi, Kie Nakamura, Akane Usami, Tomoko Tsuruta, Miki Hashimura, Toshihide Matsumoto, Makoto Saegusa
AIMS: β-catenin signaling participates in regulation of epithelial-mesenchymal transition (EMT)/cancer stem cell (CSC) properties. We focused on the role of β-catenin in resistance to neoadjuvant chemoradiotherapy in patients with rectal cancer especially pertaining to its association with EMT/CSC features. METHODS AND RESULTS: A total of 109 cases of locally advanced rectal cancer, along with a colon cancer cell line, were investigated. Nuclear β-catenin accumulation in pretreatment biopsied samples was inversely associated with therapeutic efficacy for chemoradiotherapy in resected rectal cancer...
March 28, 2017: Histopathology
https://www.readbyqxmd.com/read/28368414/tgf%C3%AE-engages-mek-erk-to-differentially-regulate-benign-and-malignant-pancreas-cell-function
#9
D R Principe, A M Diaz, C Torres, R J Mangan, B DeCant, R McKinney, M-S Tsao, A Lowy, H G Munshi, B Jung, P J Grippo
While TGFβ signals are anti-proliferative in benign and well-differentiated pancreatic cells, TGFβ appears to promote the progression of advanced cancers. To better understand dysregulation of the TGFβ pathway, we first generated mouse models of neoplastic disease with TGFβ receptor deficiencies. These models displayed reduced levels of pERK irrespective of KRAS mutation. Furthermore, exogenous TGFβ led to rapid and sustained TGFBR1-dependent ERK phosphorylation in benign pancreatic duct cells. Similar to results that our group has published in colon cancer cells, inhibition of ERK phosphorylation in duct cells mitigated TGFβ-induced upregulation of growth suppressive pSMAD2 and p21, prevented downregulation of the pro-growth signal CDK2 and ablated TGFβ-induced EMT...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28360095/hnrnpll-a-newly-identified-colorectal-cancer-metastasis-suppressor-modulates-alternative-splicing-of-cd44-during-epithelial-mesenchymal-transition
#10
Keiichiro Sakuma, Eiichi Sasaki, Kenya Kimura, Koji Komori, Yasuhiro Shimizu, Yasushi Yatabe, Masahiro Aoki
OBJECTIVE: Despite the recent advances in treatment of colon cancer, the prognosis is unfavourable for patients with distant metastases. The aim of this study was to identify targets for prevention and/or therapy of colon cancer metastasis. DESIGN: CMT93 cells, a murine rectal cancer cell line with poor metastasising activity, were transduced with lentiviral shRNA library and transplanted into the rectum of syngeneic C57BL/6 mice. Genomic DNA was collected from metastatic lesions, and the integrated shRNA were retrieved by PCR for sequencing, followed by identification of the candidate genes targeted by the shRNA...
March 30, 2017: Gut
https://www.readbyqxmd.com/read/28356122/integrated-analysis-identifies-microrna-195-as-a-suppressor-of-hippo-yap-pathway-in-colorectal-cancer
#11
Min Sun, Haibin Song, Shuyi Wang, Chunxiao Zhang, Liang Zheng, Fangfang Chen, Dongdong Shi, Yuanyuan Chen, Chaogang Yang, Zhenxian Xiang, Qing Liu, Chen Wei, Bin Xiong
BACKGROUND: With persistent inconsistencies in colorectal cancer (CRC) miRNAs expression data, it is crucial to shift toward inclusion of a "pre-laboratory" integrated analysis to expedite effective precision medicine and translational research. Aberrant expression of hsa-miRNA-195 (miR-195) which is distinguished as a clinically noteworthy miRNA has previously been observed in multiple cancers, yet its role in CRC remains unclear. METHODS: In this study, we performed an integrated analysis of seven CRC miRNAs expression datasets...
March 29, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28341962/tumour-suppressor-ep300-a-modulator-of-paclitaxel-resistance-and-stemness-is-downregulated-in-metaplastic-breast-cancer
#12
Muhammad Asaduzzaman, Stephanie Constantinou, Haoxiang Min, John Gallon, Meng-Lay Lin, Poonam Singh, Selina Raguz, Simak Ali, Sami Shousha, R Charles Coombes, Eric W-F Lam, Yunhui Hu, Ernesto Yagüe
PURPOSE: We have previously described a novel pathway controlling drug resistance, epithelial-to-mesenchymal transition (EMT) and stemness in breast cancer cells. Upstream in the pathway, three miRs (miR-106b, miR-93 and miR-25) target EP300, a transcriptional activator of E-cadherin. Upregulation of these miRs leads to the downregulation of EP300 and E-cadherin with initiation of an EMT. However, miRs regulate the expression of many genes, and the contribution to EMT by miR targets other than EP300 cannot be ruled out...
March 24, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28299802/bmp-and-notch-interaction-in-crc-subtypes
#13
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
https://www.readbyqxmd.com/read/28296190/microrna-1254-inhibits-the-migration-of-colon-adenocarcinoma-cells-by-targeting-psmd10
#14
Yi-Min Chu, Hai-Xia Peng, Ying Xu, Da-Ming Yang, Feng-Li Zhou, Rong Kuai Ji Li, Yong Lin
BACKGROUND AND AIMS: MicroRNA-1254 (miR-1254) has not been studied in colorectal cancer (CRC) to date. In the current study, we investigate the inhibitory mechanism of miR-1254 in CRC tumorigenesis. METHODS: Differential miR-1254 expression was examined using real-time-PCR in CRC and control tissues. Whether miR-1254 levels correlated with colon adenocarcinoma cell proliferation and migration was determined using the CCK-8 and transwell assays. RNA sequencing was used to identify differentially expressed genes downstream of miR-1254...
March 10, 2017: Journal of Digestive Diseases
https://www.readbyqxmd.com/read/28280353/long-non-coding-rna-ccat2-is-associated-with-poor-prognosis-in-hepatocellular-carcinoma-and-promotes-tumor-metastasis-by-regulating-snail2-mediated-epithelial-mesenchymal-transition
#15
Yongfu Xu, Binfeng Wang, Fabiao Zhang, Aidong Wang, Xuefeng Du, Peng Hu, Yu Zhu, Zheping Fang
Increasing evidence has demonstrated that aberrant expressions of long non-coding RNAs (lncRNAs) are involved in various malignancies, including hepatocellular carcinoma (HCC). This study aimed to investigate the role of lncRNA colon cancer-associated transcript 2 (CCAT2) in the progression of HCC. Quantitative real-time polymerase chain reaction analysis confirmed that CCAT2 was upregulated in HCC cell lines and cancerous tissues compared with normal liver cell line and adjacent normal tissue samples. The level of CCAT2 was positively associated with tumor-node-metastasis stages and vessel invasion...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28279784/emerging-role-of-dubs-in-tumor-metastasis-and-apoptosis-therapeutic-implication
#16
REVIEW
Mingjing He, Zhuan Zhou, George Wu, Qianming Chen, Yong Wan
Malfunction of ubiquitin-proteasome system is tightly linked to tumor formation and tumor metastasis. Targeting the ubiquitin-pathway provides a new strategy for anti-cancer therapy. Despite the parts played by ubiquitin modifiers, removal of ubiquitin from the functional proteins by the deubiquitinating enzymes (DUBs) plays an important role in governing the multiple steps of the metastatic cascade, including local invasion, dissemination, and eventual colonization of the tumor to distant organs. Both deregulated ubiquitination and deubiquitination could lead to dysregulation of various critical events and pathways such as apoptosis and epithelial-mesenchymal transition (EMT)...
March 6, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28259918/cxcl8-induces-epithelial-mesenchymal-transition-in-colon-cancer-cells-via-the-pi3k-akt-nf-%C3%AE%C2%BAb-signaling-pathway
#17
Tao Shen, Zhibin Yang, Xianshuo Cheng, Youchuan Xiao, Kun Yu, Xinyi Cai, Cuifeng Xia, Yunfeng Li
The aim of the present study was to investigate the role of chemokine (C-X-C motif) ligand 8 (CXCL8) in the proliferation, invasiveness and metastasis of colon cancer and its role in the induction of epithelial-mesenchymal transition (EMT) via activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor-κB (NF-κB) pathway. The plasmid vector containing CXCL8 cDNA was transfected into LoVo cells using Lipofectamine 2000 reagent. Real-time PCR and western blot analyses were performed to determine expression of CXCL8...
April 2017: Oncology Reports
https://www.readbyqxmd.com/read/28223538/tissue-transglutaminase-induces-epithelial-mesenchymal-transition-and-the-acquisition-of-stem-cell-like-characteristics-in-colorectal-cancer-cells
#18
Oluseyi Ayinde, Zhuo Wang, Martin Griffin
Human colon cancer cell lines (CRCs) RKO, SW480 and SW620 were investigated for TG2 involvement in tumour advancement and aggression. TG2 expression correlated with tumour advancement and expression of markers of epithelial-mesenchymal transition (EMT). The metastatic cell line SW620 showed high TG2 expression compared to the primary tumour cell lines SW480 and RKO and could form tumour spheroids under non- adherent conditions. TG2 manipulation in the CRCs by shRNA or TG2 transduction confirmed the relationship between TG2 and EMT...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28202525/oncogenic-effects-of-high-mapk-activity-in-colorectal-cancer-mark-progenitor-cells-and-persist-irrespective-of-ras-mutations
#19
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/28192397/downregulation-of-mir-218-contributes-to-epithelial-mesenchymal-transition-and-tumor-metastasis-in-lung-cancer-by-targeting-slug-zeb2-signaling
#20
Z-M Shi, L Wang, H Shen, C-F Jiang, X Ge, D-M Li, Y-Y Wen, H-R Sun, M-H Pan, W Li, Y-Q Shu, L-Z Liu, S C Peiper, J He, B-H Jiang
Epithelial-mesenchymal transition (EMT) has been recognized as a key element of cell migration and invasion in lung cancer; however, the underlying mechanisms are not fully elucidated. Recently, emerging evidence suggest that miRNAs have crucial roles in control of EMT and EMT-associated traits such as migration, invasion and chemoresistance. Here, we found that miR-218 expression levels were significantly downregulated in lung cancer tissues compared with adjacent non-cancerous tissues, and the levels of miR-218 were significantly associated with histological grades and lymph node metastasis...
February 13, 2017: Oncogene
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