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colorectal cancer And cancer stem cell

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https://www.readbyqxmd.com/read/28739799/lgr5-receptor-promotes-cell-cell-adhesion-in-stem-cells-and-colon-cancer-cells-via-the-iqgap1-rac1-pathway
#1
Kendra S Carmon, Xing Gong, Jing Yi, Ling Wu, Anthony Thomas, Catherine M Moore, Ikuo Masuho, David J Timson, Kirill A Martemyanov, Qingyun J Liu
Leucine rich repeat containing G protein coupled receptor 5 (LGR5) is a bona fide marker of adult stem cells in several epithelial tissues, most notably in the intestinal crypts and is highly upregulated in many colorectal, hepatocellular, and ovarian cancers. LGR5 activation by R-spondin (RSPO) ligands potentiates Wnt/β-catenin signaling in vitro, yet deletion of LGR5 in stem cells has little or no effect on Wnt/β-catenin signaling or cell proliferation in vivo. Remarkably, modulation of LGR5 expression has a major impact on the actin cytoskeletal structure and cell adhesion in the absence of RSPO stimulation, but the molecular mechanism is unclear...
July 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28739692/wnt-%C3%AE-catenin-signaling-inhibitor-ic-2-suppresses-sphere-formation-and-sensitizes-colorectal-cancer-cells-to-5-fluorouracil
#2
Shoichi Urushibara, Toshiaki Tsubota, Ryoma Asai, Junya Azumi, Keigo Ashida, Yoshiyuki Fujiwara, Goshi Shiota
BACKGROUND/AIM: Colorectal cancer (CRC) is one of the most malignant types of cancer worldwide. Recent studies suggest that a small subpopulation of cells, so-called cancer stem cells (CSCs), promote the high metastasis and relapse associated with CRC. WNT/β-catenin signaling plays a critical role in CSC maintenance. Therefore, its inhibitor may suppress CSCs and improve therapeutic effects on CRC. MATERIALS AND METHODS: The effects of a derivative of WNT/β-catenin signaling inhibitor, IC-2, which we recently developed, on the CRC cell line DLD-1, were examined by luciferase reporter assay, WST assay, western blot, and sphere assay...
August 2017: Anticancer Research
https://www.readbyqxmd.com/read/28732600/hierarchy-and-plasticity-in-the-intestinal-stem-cell-compartment
#3
REVIEW
Maryam Yousefi, Linheng Li, Christopher J Lengner
Somatic stem cells maintain tissue homeostasis by organizing themselves in such a way that they can maintain proliferative output while simultaneously protecting themselves from DNA damage that may lead to oncogenic transformation. There is considerable debate about how such stem cell compartments are organized. Burgeoning evidence from the small intestine and colon provides support for a two-stem cell model involving an actively proliferating but injury-sensitive stem cell and a rare, injury-resistant pool of quiescent stem cells...
July 18, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28731184/bufalin-reverses-acquired-drug-resistance-by-inhibiting-stemness-in-colorectal-cancer-cells
#4
Jian Sun, Ke Xu, Yanyan Qiu, Hong Gao, Jianhua Xu, Qingfeng Tang, Peihao Yin
Drug resistance is an obstacle to chemotherapy in tumor patients. Recent studies have shown that the high stemness of cancer cells may be induced by chemotherapeutic drugs, which is correlated with drug resistance. In the present study, we investigated the effects of bufalin on the stemness of colorectal cancer. We found that cisplatin could induce high stemness through the tumorsphere formation assay in vitro and in vivo in the colorectal cancer cell lines HCT116 and LoVo. In addition, cisplatin-treated tumorsphere cells showed drug‑resistant properties...
July 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28731148/molecular-genetics-and-targeted-therapy-of-wnt-related-human-diseases-review
#5
Masuko Katoh, Masaru Katoh
Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription...
July 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28724889/aptamer-mediated-survivin-rnai-enables-5-fluorouracil-to-eliminate-colorectal-cancer-stem-cells
#6
Hadi AlShamaileh, Tao Wang, Dongxi Xiang, Wang Yin, Phuong Ha-Lien Tran, Roberto A Barrero, Pei-Zhuo Zhang, Yong Li, Lingxue Kong, Ke Liu, Shu-Feng Zhou, Yingchun Hou, Sarah Shigdar, Wei Duan
The development of chemoresistance and inability in elimination of cancer stem cells are among the key limitations of cancer chemotherapy. Novel molecular therapeutic strategies able to overcome such limitations are urgently needed for future effective management of cancer. In this report, we show that EpCAM-aptamer-guided survivin RNAi effectively downregulated survivin both in colorectal cancer cells in vitro and in a mouse xenograft model for colorectal cancer. When combined with the conventional chemotherapeutic agents, the aptamer-guided survivin RNAi was able to enhance the sensitivity towards 5-FU or oxaliplatin in colorectal cancer stem cells, increase apoptosis, inhibit tumour growth and improve the overall survival of mice bearing xenograft colorectal cancer...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720124/defining-the-role-of-lgr5-stem-cells-in-colorectal-cancer-from-basic-research-to-clinical-applications
#7
Masayuki Fujii, Toshiro Sato
Intestinal epithelium is structured by two distinct components: the villi and the crypts. The crypts harbor stem cells expressing Lgr5 and thus have been a representative model to study tissue stem cell functions. Recent advances in organoid technology and analytical modalities have enabled precise characterization of Lgr5(+) intestinal stem cells, providing insights into their roles in homeostasis and cancer.
July 18, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28718412/stem-cells-cancer-and-musashi-in-blood-and-guts
#8
REVIEW
Michael G Kharas, Christopher J Lengner
The mammalian MSI family of RNA-binding proteins (RBPs) have important roles as oncoproteins in an array of tumor types, including leukemias, glioblastomas, and pancreatic, breast, lung, and colorectal cancers. The mammalian Msi genes, Msi1 and Msi2, have been most thoroughly investigated in two highly proliferative tissues prone to oncogenic transformation: the hematopoietic lineage and the intestinal epithelium. Despite their vast phenotypic differences, MSI proteins appear to have an analogous role in governing the stem cell compartment in both of these tissues, potentially providing a paradigm for a broader understanding of MSI function and oncogenic activities...
May 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28716720/met-signaling-mediates-intestinal-crypt-villus-development-regeneration-and-adenoma-formation-and-is-promoted-by-stem-cell-cd44-isoforms
#9
Sander P J Joosten, Jurrit Zeilstra, Harmen van Andel, R Clinton Mijnals, Joost Zaunbrecher, Annet A M Duivenvoorden, Marc van de Wetering, Hans Clevers, Marcel Spaargaren, Steven T Pals
BACKGROUND & AIMS: Resistance of metastatic human colorectal cancer cells to drugs that block epidermal growth factor receptor (EGFR) signaling could be caused by aberrant activity of other receptor tyrosine kinases, activating overlapping signaling pathways. One of these receptor tyrosine kinases could be MET, the receptor for hepatocyte growth factor (HGF). We investigated how MET signaling, and its interaction with CD44 (a putative MET co-receptor regulated by Wnt signaling and highly expressed by intestinal stem cells [ISCs] and adenomas) affects intestinal homeostasis, regeneration, and adenoma formation in mini-gut organoids and mice...
July 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28708826/intestinal-stem-cell-overproliferation-resulting-from-inactivation-of-the-apc-tumor-suppressor-requires-the-transcription-cofactors-earthbound-and-erect-wing
#10
Ai Tian, Hassina Benchabane, Zhenghan Wang, Chloe Zimmerman, Nan Xin, Jessica Perochon, Gabriela Kalna, Owen J Sansom, Chao Cheng, Julia B Cordero, Yashi Ahmed
Wnt/β-catenin signal transduction directs intestinal stem cell (ISC) proliferation during homeostasis. Hyperactivation of Wnt signaling initiates colorectal cancer, which most frequently results from truncation of the tumor suppressor Adenomatous polyposis coli (APC). The β-catenin-TCF transcription complex activates both the physiological expression of Wnt target genes in the normal intestinal epithelium and their aberrantly increased expression in colorectal tumors. Whether mechanistic differences in the Wnt transcription machinery drive these distinct levels of target gene activation in physiological versus pathological states remains uncertain, but is relevant for the design of new therapeutic strategies...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28708138/blocking-endothelin-1-receptor-%C3%AE-catenin-circuit-sensitizes-to-chemotherapy-in-colorectal-cancer
#11
Roberta Cianfrocca, Laura Rosanò, Piera Tocci, Rosanna Sestito, Valentina Caprara, Valeriana Di Castro, Ruggero De Maria, Anna Bagnato
The limited clinical response to conventional chemotherapeutics observed in colorectal cancer (CRC) may be related to the connections between the hyperactivated β-catenin signaling and other pathways in CRC stem-like cells (CRC-SC). Here, we show the mechanistic link between the endothelin-1 (ET-1)/ET-1 receptor (ET-1R) signaling and β-catenin pathway through the specific interaction with the signal transducer β-arrestin1 (β-arr1), which initiates signaling cascades as part of the signaling complex. Using a panel of patient-derived CRC-SC, we show that these cells secrete ET-1 and express ETAR and β-arr1, and that the activation of ETAR/β-arr1 axis promotes the cross-talk with β-catenin signaling to sustain stemness, epithelial-to-mesenchymal transition (EMT) phenotype and response to chemotherapy...
July 14, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28699179/colorectal-cancer-stem-cells-acquire-chemoresistance-through-the-upregulation-of-fbxw7-and-the-consequent-degradation-of-c-myc
#12
Daisuke Izumi, Takatsugu Ishimoto, Keisuke Miyake, Tsugio Eto, Kota Arima, Yuki Kiyozumi, Tomoyuki Uchihara, Junji Kurashige, Masaaki Iwatsuki, Yoshifumi Baba, Yasuo Sakamoto, Yuji Miyamoto, Naoya Yoshida, Masayuki Watanabe, Ajay Goel, Patrick Tan, Hideo Baba
The cancer stem cell (CSC) paradigm suggests that tumors are organized hierarchically. We previously established an LGR5(+) human colorectal cancer stem-cell-enriched cell line (colorectal CSCs) that expresses well-accepted colorectal CSC markers and that can dynamically switch between proliferative and drug-resistant non-cycling states. We performed this study to elucidate the molecular mechanisms responsible for evading cell death in colorectal CSCs mediated by anticancer agents. During the cell cycle arrest caused by anticancer agents, we found that c-Myc expression was substantially decreased in colorectal CSCs...
July 11, 2017: Stem Cells
https://www.readbyqxmd.com/read/28693796/regulatory-effects-of-berberine-on-micrornome-in-cancer-and-other-conditions
#13
REVIEW
Seyed Hasan Ayati, Badrieh Fazeli, Amir Abbas Momtazi-Borojeni, Arrigo F G Cicero, Matteo Pirro, Amirhossein Sahebkar
Berberine (BBR) is an isoquinoline alkaloid found in different plant families such as Berberidaceae, Ranunculaceae, and Papaveraceae. BBR is well-known for its anti-inflammatory, lipid-modifying, anticancer, anti-diabetic, antibacterial, antiparasitic and fungicide activities. Multiple pharmacological actions of BBR stem from different molecular targets of this phytochemical. MicroRNAs (miRs) are single-stranded, evolutionary conserved, small non-coding RNA molecules with a length of 19-23 nucleotides that are involved in RNA silencing and post-transcriptional regulation of gene expression through binding to the 3'-untranslated region (3'UTR) of target mRNA...
August 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28677737/expression-of-epithelial-mesenchymal-transition-and-cancer-stem-cell-markers-in-colorectal-adenocarcinoma-clinicopathological-significance
#14
Ji Eun Choi, Jun Sang Bae, Myoung Jae Kang, Myoung Ja Chung, Kyu Yun Jang, Ho Sung Park, Woo Sung Moon
Epithelial-mesenchymal transition (EMT) is known to be associated with cancer progression, metastatic spread, and therapeutic resistance and to occur at the invasive front. Cancer stem cells (CSCs) display stemness features and might be implicated in tumor initiation, local recurrence and metastasis. The present study was conducted to examine the expression status and relationships between EMT- and CSC-related proteins in the different tumor areas of primary colorectal cancer (CRC), along with their clinicopathological significance...
July 5, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28676732/proinflammatory-cytokines-il-6-and-tnf-%C3%AE-increased-telomerase-activity-through-nf-%C3%AE%C2%BAb-stat1-stat3-activation-and-withaferin-a-inhibited-the-signaling-in-colorectal-cancer-cells
#15
Seyung S Chung, Yong Wu, Quincy Okobi, Debbie Adekoya, Mohammad Atefi, Orette Clarke, Pranabananda Dutta, Jaydutt V Vadgama
There are increasing evidences of proinflammatory cytokine involvement in cancer development. Here, we found that two cytokines, IL-6 and TNF-α, activated colorectal cancer cells to be more invasive and stem-like. Combined treatment of IL-6 and TNF-α phosphorylated transcription factors STAT3 in a synergistic manner. STAT3, STAT1, and NF-κB physically interacted upon the cytokine stimulation. STAT3 was bound to the promoter region of human telomerase reverse transcriptase (hTERT). IL-6 and TNF-α stimulation further enhanced STAT3 binding affinity...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28670499/wnt-signaling-pathway-protein-lef1-in-cancer-as-a-biomarker-for-prognosis-and-a-target-for-treatment
#16
REVIEW
Larion Santiago, Garrett Daniels, Dongwen Wang, Fang-Ming Deng, Peng Lee
Transcription factors are regulatory proteins that either activate or repress the transcription of genes via binding to DNA regulatory sequences and regulating recruitment of transcriptional complexes. Lymphoid enhancer-binding factor 1 (LEF1), a member of the T-cell Factor (TCF)/LEF1 family of high-mobility group transcription factors, is a downstream mediator of the Wnt/β-catenin signaling pathway, but can also modulate gene transcription independently. LEF1 is essential in stem cell maintenance and organ development, especially in its role in epithelial-mesenchymal transition (EMT) by activating the transcription of hallmark EMT effectors including N-Cadherin, Vimentin, and Snail...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28652251/hypoxia-induced-downregulation-of-dusp-2-phosphatase-drives-colon-cancer-stemness
#17
Pei-Chi Hou, Yo-Hua Li, Shih-Chieh Lin, Shao-Chieh Lin, Jenq-Chang Lee, Bo-Wen Lin, Jing-Ping Liou, Jang-Yang Chang, Ching-Chuan Kuo, Yi-Min Liu, H Sunny Sun, Shaw-Jenq Tsai
Cancer stem-like cells (CSC) evolve to overcome the pressures of reduced oxygen, nutrients or chemically induced cell death, but the mechanisms driving this evolution are incompletely understood. Here we report that hypoxia-mediated downregulation of the dual specificity phosphatase 2 (DUSP2) is critical for the accumulation of CSC in colorectal cancer. Reduced expression of DUSP2 led to overproduction of cyclooxygenase-2 (COX-2)-derived prostaglandin E2, which promoted cancer stemness via the EP2/EP4 signaling pathways...
June 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/28639895/upregulation-of-mir-199a-b-contributes-to-cisplatin-resistance-via-wnt-%C3%AE-catenin-abcg2-signaling-pathway-in-aldha1-colorectal-cancer-stem-cells
#18
Binghe Chen, Dezhong Zhang, Jun Kuai, Mingkun Cheng, Xiangjie Fang, Guangyan Li
Cisplatin resistance in colorectal cancer largely results from the colorectal cancer stem cells which could be targeted to improve the efficacy of chemotherapy. MicroRNAs are possible modulators of cancer stem cell characteristics and maybe involved in the retention of cancer stem cell chemoresistance. The aim of this study was to investigate the biological function of miR-199a/b on cisplatin resistance in colorectal cancer stem cells and its related mechanisms. Here, ALDHA1(+) cells from primary colorectal cancer tissues behaved similar to cancer stem cells and were chemoresistant to cisplatin...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28638460/zeb1-mediates-drug-resistance-and-emt-in-p300-deficient-crc
#19
Darina Lazarova, Michael Bordonaro
We discuss the hypothesis that ZEB1-Wnt-p300 signaling integrates epithelial to mesenchymal transition (EMT) and resistance to histone deacetylase inhibitors (HDACis) in colorectal cancer (CRC) cells. The HDACi butyrate, derived from dietary fiber, has been linked to CRC prevention, and other HDACis have been proposed as therapeutic agents against CRC. We have previously discussed that resistance to butyrate likely contributes to colonic carcinogenesis, and we have demonstrated that butyrate resistance leads to cross-resistance to cancer therapeutic HDACis...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28634417/expression-status-of-piwil1-as-a-prognostic-marker-of-colorectal-cancer
#20
Rui Sun, Chun-Li Gao, Dong-Hai Li, Bo-Jun Li, Yan-Hong Ding
The PIWI-like protein 1 (PIWIL1) plays a crucial role in stem cell proliferation, embryogenesis, growth, and development, as well as differentiation and maturation in multiple organisms. The relationships between PIWIL1 expression and clinicopathological features of colorectal cancer (CRC) patients were analyzed by us. Survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. The high expression rate of PIWIL1 in the cancer tissue was obviously higher than that in the corresponding adjacent tissue...
2017: Disease Markers
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