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https://www.readbyqxmd.com/read/28546516/re-evaluating-the-role-of-epithelial-mesenchymal-transition-in-cancer-progression
#1
Andrew Sulaiman, Zemin Yao, Lisheng Wang
Epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) are essential for embryonic development and also important in cancer progression. In a conventional model, epithelial-like cancer cells transit to mesenchymal-like tumor cells with great motility via EMT transcription factors; these mesenchymal-like cells migrate through the circulation system, relocate to a suitable site and then convert back to an epithelial-like phenotype to regenerate the tumor. However, recent findings challenge this conventional model and support the existence of a stable hybrid epithelial/mesenchymal (E/M) tumor population...
April 6, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28521303/emt-circulating-tumor-cells-detected-by-cell-surface-vimentin-are-associated-with-prostate-cancer-progression
#2
Arun Satelli, Izhar Batth, Zachary Brownlee, Abhishek Mitra, Shouhao Zhou, Hyangsoon Noh, Christina R Rojas, Heming Li, Qing H Meng, Shulin Li
Recent advances in the field of circulating tumor cells (CTC) have shown promise in this liquid biopsy-based prognosis of patient outcome. However, not all of the circulating cells are tumor cells, as evidenced by a lack of tumor-specific markers. The current FDA standard for capturing CTCs (CellSearch) relies on an epithelial marker and cells captured via CellSearch cannot be considered to have undergone EMT. Therefore, it is difficult to ascertain the presence and relevance of any mesenchymal or EMT-like CTCs...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28513825/loss-of-tet1-facilitates-dld1-colon-cancer-cell-migration-via-h3k27me3-mediated-down-regulation-of-e-cadherin
#3
Zhen Zhou, Hong-Sheng Zhang, Yang Liu, Zhong-Guo Zhang, Guang-Yuan Du, Hu Li, Xiao-Ying Yu, Ying-Hui Huang
Epigenetic modifications such as histone modifications and cytosine hydroxymethylation are linked to tumorigenesis. Loss of 5-hydroxymethylcytosine (5hmC) by ten-eleven translocation 1 (TET1) down-regulation facilitates tumor initiation and development. However, the mechanisms by which loss of TET1 knockdown promotes malignancy development remains unclear. Here, we report that TET1 knockdown induced epithelial-mesenchymal transition (EMT) and increased cancer cell growth, migration and invasion in DLD1 cells...
May 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28488579/evolutionary-cancer-favoring-engineered-vaccinia-virus-for-metastatic-hepatocellular-carcinoma
#4
So Young Yoo, Su-Nam Jeong, Dae Hwan Kang, Jeong Heo
Engineered vaccinia virus-based therapy shows promising results in patients with advanced hepatocellular carcinoma, although a strategic virus design for the metastatic liver and the study of its efficacy in treating the cancer has not been well assessed. In this paper, we proposed a simple and strategic virus design for targeting metastatic hepatocellular carcinoma. We developed an evolutionary cancer-favoring engineered vaccinia virus (CVV, which is produced by repeated selective replication in cancerous tissues and then deleting viral thymidine kinase genes) and investigated its therapeutic effects on metastatic liver cancer...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28487386/an-mirna-expression-signature-for-the-human-colonic-stem-cell-niche-distinguishes-malignant%C3%A2-from-normal-epithelia
#5
Vignesh Viswanathan, Shirish Damle, Tao Zhang, Lynn M Opdenaker, Shirin Modarai, Monica Accerbi, Skye Schmidt, Pamela J Green, Deni Galileo, Juan P Palazzo, Jeremy Fields, Sepehr Haghighat, Isidore Rigoutsos, Gregory E Gonye, Bruce M Boman
Malignant transformation of tissue stem cells may be the root of most cancer. Accordingly, we identified miRNA expression patterns in the normal human colonic stem cell (SC) niche to understand how cancer stem cells (CSCs) may arise. In profiling miRNA expression in SC-enriched crypt subsections isolated from fresh, normal surgical specimens, we identified 16 miRNAs that were differentially expressed in the crypt bottom, creating a SC signature for normal colonic epithelia (NCE). A parallel analysis of colorectal cancer (CRC) tissues showed differential expression of 83 miRNAs relative to NCE...
May 9, 2017: Cancer Research
https://www.readbyqxmd.com/read/28475287/lncrna-ccat1-promotes-glioma-tumorigenesis-by-sponging-mir-181b
#6
Bingzhou Cui, Baoshan Li, Qi Liu, Youqiang Cui
Colon cancer-associated transcript 1 (CCAT1), a long non-coding RNA (lncRNA), is upregulated and has a vital role in the pathogenesis of numerous cancers. Recently, its high expression was found in glioma tissues. miR-181b is downregulated in glioma and acts as a tumor suppressor. However, the exact mechanism of CCAT1 action in the regulation of glioma development remains unknown. CCAT1 and miR-181b expression was firstly examined in glioma tissue samples by real-time PCR. An RNA interference approach was used to downregulate CCAT1 expression and we analyzed the underlying mechanism of CCAT1 by using bioinformatics analysis, CCK-8 assay, Transwell assay, flow cytometry, luciferase assay, RNA immunoprecipitation, real-time PCR, Western blot, and xenograft models...
May 5, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28435028/antagonistic-effects-of-p53-and-hif1a-on-microrna-34a-regulation-of-ppp1r11-and-stat3-and-hypoxia-induced-epithelial-to-mesenchymal-transition-in-colorectal-cancer-cells
#7
Huihui Li, Matjaz Rokavec, Longchang Jiang, David Horst, Heiko Hermeking
BACKGROUND & AIMS: In colorectal tumors, hypoxia causes resistance to therapy and promotes metastasis. Loss of the tumor suppressor p53 (encoded by TP53) provides cancer cells with a selective advantage under conditions of hypoxia, but little is known about the mediators of this effect. METHODS: Isogenic CRC cell lines with different TP53 genotypes were placed under conditions of hypoxia. We examined the effects on levels and activity of microRNA-34 a (MIR34A) in CRC cells...
April 20, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28433772/mesenchymal-stem-cells-induce-epithelial-to-mesenchymal-transition-in-colon-cancer-cells-through-direct-cell-to-cell-contact
#8
Hidehiko Takigawa, Yasuhiko Kitadai, Kei Shinagawa, Ryo Yuge, Yukihito Higashi, Shinji Tanaka, Wataru Yasui, Kazuaki Chayama
We previously reported that in an orthotopic nude mouse model of human colon cancer, bone marrow-derived mesenchymal stem cells (MSCs) migrated to the tumor stroma and promoted tumor growth and metastasis. Here, we evaluated the proliferation and migration ability of cancer cells cocultured with MSCs to elucidate the mechanism of interaction between cancer cells and MSCs. Proliferation and migration of cancer cells increased following direct coculture with MSCs but not following indirect coculture. Thus, we hypothesized that direct contact between cancer cells and MSCs was important...
May 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28433181/effects-of-scutellaria-barbata-polysaccharide-on-the-proliferation-apoptosis-and-emt-of-human-colon-cancer-ht29-cells
#9
Pengda Sun, Dong Sun, Xudong Wang
A water-soluble polysaccharide SPS2p was isolated from the whole grass of Scutellaria barbata and SPS2p contained 53.6% carbohydrates, 38.5% uronic acid and 8.2% proteins. The molecular weight of SPS2p showed only one molecular weight distribution (2.6×10(4)Da) and the monosaccharide composition of SPS2p showed the presence of arabinose, mannose, glucose and galactose at the ratio of 1.31:1.00:3.59:1.59. The results showed that SPS2p could improve the proliferation inhibition rate; SPS2p could also elevate apoptosis rate, apoptosis index and the levels of Bax and Bak, but lower levels of Bcl-2 and FN; SPS2p could up-regulate the expression of E-cadherin mRNA, and down-regulate the expressions of N-cadherin and vimentin mRNA, and the ratio of p-AKT/AKT in HT29 cells...
July 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28431931/peroxiredoxin-5-promotes-the-epithelial-mesenchymal-transition-in-colon-cancer
#10
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...
June 3, 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
#11
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...
May 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
#12
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...
May 9, 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
#13
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
#14
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...
May 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28407379/epithelial-mesenchymal-plasticity-and-circulating-tumor-cells-travel-companions-to-metastases
#15
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
#16
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
#17
Hiroyuki Takahashi, Kie Nakamura, Akane Usami, Tomoko Tsuruta, Miki Hashimura, Toshihide Matsumoto, Makoto Saegusa
AIMS: β-Catenin signalling participates in the regulation of epithelial-mesenchymal transition (EMT)/cancer stem cell (CSC) properties. The aim of this study was to investigate 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...
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
#18
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
#19
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
#20
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
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