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colorectal cancer And cancer stem cell

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https://www.readbyqxmd.com/read/28915668/nsc30049-inhibits-chk1-pathway-in-5-fu-resistant-crc-bulk-and-stem-cell-populations
#1
Satya Narayan, Aruna S Jaiswal, Ritika Sharma, Akbar Nawab, Lizette Vila Duckworth, Brian K Law, Maria Zajac-Kaye, Thomas J George, Jay Sharma, Arun K Sharma, Robert A Hromas
The 5-fluorouracil (5-FU) treatment induces DNA damage and stalling of DNA replication forks. These stalled replication forks then collapse to form one sided double-strand breaks, leading to apoptosis. However, colorectal cancer (CRC) stem cells rapidly repair the stalled/collapsed replication forks and overcome treatment effects. Recent evidence suggests a critical role of checkpoint kinase 1 (Chk1) in preventing the replicative stress. Therefore, Chk1 kinase has been a target for developing mono or combination therapeutic agents...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915611/metformin-increases-chemo-sensitivity-via-gene-downregulation-encoding-dna-replication-proteins-in-5-fu-resistant-colorectal-cancer-cells
#2
Sung-Hee Kim, Soon-Chan Kim, Ja-Lok Ku
Metformin is most widely prescribed for type 2 diabetes. Recently, evidences have shown that metformin has anticancer effects on pancreatic-, colorectal-, ovarian-, and other cancers. Because metformin has less adverse effects and is inexpensive, it could be a useful chemo-therapeutic agent with anticancer effects. In this study, we demonstrated metformin inhibited by cell proliferation, cell migration ability, clonogenic ability, and cancer stem cell population. Metformin also induced cell cycle arrest in parental-(SNU-C5), and 5-Fu resistant-colorectal cancer cell line (SNU-C5_5FuR)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912133/use-of-crispr-modified-human-stem-cell-organoids-to-study-the-origin-of-mutational-signatures-in-cancer
#3
Jarno Drost, Ruben van Boxtel, Francis Blokzijl, Tomohiro Mizutani, Nobuo Sasaki, Valentina Sasselli, Joep de Ligt, Sam Behjati, Judith E Grolleman, Tom van Wezel, Serena Nik-Zainal, Roland P Kuiper, Edwin Cuppen, Hans Clevers
Mutational processes underlie cancer initiation and progression. Signatures of these processes in cancer genomes may explain cancer etiology, and hold diagnostic and prognostic value. Here, we develop a strategy that can be used to explore the origin of cancer-associated mutational signatures. We used CRISPR/Cas9 technology to delete key DNA repair genes in human colon organoids, followed by delayed sub-cloning and whole-genome sequencing. We found that mutation accumulation in organoids deficient in the mismatch repair gene MLH1 is driven by replication errors and accurately models the mutation profiles observed in mismatch repair-deficient colorectal cancers...
September 14, 2017: Science
https://www.readbyqxmd.com/read/28910694/an-epidemiologic-perspective-on-the-stem-cell-hypothesis-in-human-carcinogenesis
#4
REVIEW
David Schottenfeld
BACKGROUND: Tomasetti and Vogelstein have hypothesized that the patterns of cancer incidence in various cells and tissues are highly correlated with the estimated lifetime number of stem cell divisions. The authors reviewed the risks in tissues of 17 types of cancer from the United States and 69 additional countries. Positive correlations were observed consistently between the tissue - specific cancer incidence and the estimated lifetime number of stem cell divisions. The authors concluded that approximately two-thirds of global cancer incidence may be attributed to random DNA replication errors...
September 11, 2017: Cancer Epidemiology
https://www.readbyqxmd.com/read/28910490/regulation-of-wnt-%C3%AE-catenin-signalling-by-tankyrase-dependent-poly-adp-ribosyl-ation-and-scaffolding
#5
REVIEW
Laura Mariotti, Katie Pollock, Sebastian Guettler
The Wnt/β-catenin signalling pathway is pivotal for stem cell function and the control of cellular differentiation, both during embryonic development and tissue homeostasis in adults. Its activity is carefully controlled through the concerted interactions of concentration-limited pathway components and a wide range of posttranslational modifications, including phosphorylation, ubiquitylation, sumoylation, poly(ADP-ribosyl)ation (PARylation) and acetylation. Regulation of Wnt/β-catenin signalling by PARylation was discovered relatively recently...
September 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28887549/satb2-%C3%AE-catenin-tcf-lef-pathway-induces-cellular-transformation-by-generating-cancer-stem-cells-in-colorectal-cancer
#6
Wei Yu, Yiming Ma, Sharmila Shankar, Rakesh K Srivastava
Recent studies have demonstrated the involvement of colorectal cancer (CRC) stem cells (CSC) in transformation, cancer progression and metastasis. The main goal of this paper was to examine the molecular mechanisms by which SATB2 induced malignant transformation of colorectal epithelial cells. SATB2 induced malignant transformation and these transformed cells gained the characteristics of CSCs by expressing stem cell markers (CD44, CD133, LGR5 and DCLK1) and transcription factors (c-Myc, Nanog and Sox2). Overexpression of SATB2 in normal colorectal epithelial cells increased cell motility, migration and invasion, which were associated with an increase in N-cadherin and Zeb1, and decrease in E-cadherin expression...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28881738/expression-analysis-of-microrna-as-prognostic-biomarkers-in-colorectal-cancer
#7
Jie Yang, Dongling Ma, Andrew Fesler, Haiyan Zhai, Apisri Leamniramit, Wenzhe Li, Song Wu, Jingfang Ju
microRNA (miRNA) based biomarkers have unique advantages due to their critical regulatory function, superior stability, and relatively small number compared to mRNAs. A number of miRNAs play key roles in colon cancer stem cell chemoresistance and have clinical potential as prognostic biomarkers. The purpose of this study is to systematically validate the prognostic potential of miRNAs in colorectal cancer. In this study, we validated the prognostic potential of a panel of miRNAs using 205 stage II, III, and IV colorectal cancer specimens by qRT-PCR analysis...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28880275/lgr5-promotes-cancer-stem-cell-traits-and-chemoresistance-in-cervical-cancer
#8
Hao-Zhe Cao, Xiao-Fang Liu, Wen-Ting Yang, Qing Chen, Peng-Sheng Zheng
Cancer stem cells (CSCs), also known as tumor-initiating cells, contribute to tumorigenesis, resistance to chemoradiotherapy and recurrence in human cancers, suggesting targeting CSCs may represent a potential therapeutic strategy. Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) has recently been found to be a bona fide marker of colorectal CSCs. Our previous study showed that LGR5 functions as a tumor promoter in cervical cancer by activating the Wnt/β-catenin pathway. However, very little is known about the function or contribution of LGR5 to cervical CSCs...
September 7, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28870287/stress-responsive-mir-31-is-a-major-modulator-of-mouse-intestinal-stem-cells-during-regeneration-and-tumorigenesis
#9
Yuhua Tian, Xianghui Ma, Cong Lv, Xiaole Sheng, Xiang Li, Ran Zhao, Yongli Song, Thomas Andl, Maksim V Plikus, Jinyue Sun, Fazheng Ren, Jianwei Shuai, Christopher J Lengner, Wei Cui, Zhengquan Yu
Intestinal regeneration and tumorigenesis are believed to be driven by intestinal stem cells (ISCs). Elucidating mechanisms underlying ISC activation during regeneration and tumorigenesis can help uncover the underlying principles of intestinal homeostasis and disease including colorectal cancer. Here we show that miR-31 drives ISC proliferation, and protects ISCs against apoptosis, both during homeostasis and regeneration in response to ionizing radiation injury. Furthermore, miR-31 has oncogenic properties, promoting intestinal tumorigenesis...
September 5, 2017: ELife
https://www.readbyqxmd.com/read/28869601/role-of-smad-proteins-in-colitis-associated-cancer-from-known-to-the-unknown
#10
REVIEW
P Chandrasinghe, B Cereser, M Moorghen, I Al Bakir, N Tabassum, A Hart, J Stebbing, J Warusavitarne
Small mothers against decapentaplegic (SMAD) proteins are a family of signal transduction molecules in transforming growth factor β (TGFβ) ligand pathways that have been found to have a key role in the pathogenesis of inflammatory bowel disease (IBD). Long standing IBD predisposes individuals to colitis-associated colorectal cancer (CAC), an entity that possess unique characteristics compared to hereditary and sporadic cancer. The ligands of the TGFβ super family along with SMADs have also been implicated in several aspects of colorectal cancer formation...
September 4, 2017: Oncogene
https://www.readbyqxmd.com/read/28864417/tif1%C3%AE-is-phosphorylated-at-serine-473-in-colorectal-tumor-cells-through-p38-mitogen-activated-protein-kinase-as-an-oxidative-defense-mechanism
#11
Larina Tzu-Wei Shen, Han-Yi E Chou, Mitsuyasu Kato
TIF1β is a pleiotropic regulator of a diverse range of cellular processes such as DNA repair or gene repression in stem cells. This functional switch depends on phosphorylation at serine residue 473 and multiple pathways exist to accomplish this. However, the effects of exogenous reactive oxygen species (ROS) generated by bacterial flora and dietary metabolites in the colonic lumen or chemotherapy on TIF1β have not been determined. We report here that exposure of colorectal cancer (CRC) cell lines DLD-1 and HCT116 to hydrogen peroxide specifically induces TIF1β Ser473 phosphorylation...
August 30, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28862656/bromopropane-compounds-increase-the-stemness-of-colorectal-cancer-cells
#12
Young-Chang Cho, Thanh Thi Nguyen, So-Yeon Park, Kwonseop Kim, Hyung Sik Kim, Hye Gwang Jeong, Kyung Keun Kim, Hangun Kim
Bromopropane (BP) compounds, including 1-bromopropane, 2-bromopropane, and 1,2-dibromopropane, are used in industry for various purposes, and their deleterious effects on human health are becoming known. In this study, we examined the effects of BP compounds on the stemness of colorectal cancer cells. At low, non-cytotoxic concentrations, BP compounds significantly increased spheroid formation in CSC221, DLD1, Caco2, and HT29 cells. In addition, the levels of cancer stem cell markers, such as aldehyde dehydrogenase-1, cluster of differentiation 133 (CD133), CD44, Lgr5, Musashi-1, Ephrin receptor, and Bmi-1 increased after exposure to BP compounds...
September 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28854245/mir-625-3p-is-upregulated-in-cd8-t-cells-during-early-immune-reconstitution-after-allogeneic-stem-cell-transplantation
#13
Kriti Verma, Nidhi Jyotsana, Ivonne Buenting, Susanne Luther, Angelika Pfanne, Thomas Thum, Arnold Ganser, Michael Heuser, Eva M Weissinger, Lothar Hambach
Alloreactive CD8+ T-cells mediate the curative graft-versus-leukaemia effect, the anti-viral immunity and graft-versus-host-disease (GvHD) after allogeneic stem cell transplantation (SCT). Thus, immune reconstitution with CD8+ T-cells is critical for the outcome of patients after allogeneic SCT. Certain miRNAs such as miR-146a or miR-155 play an important role in the regulation of post-transplant immunity in mice. While some miRNAs e.g. miR-423 or miR-155 are regulated in plasma or full blood during acute GvHD also in man, the relevance and expression profile of miRNAs in T-cells after allogeneic SCT is unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28854096/targeting-the-colorectal-cancer-stem-cell
#14
Jan Paul Medema
New England Journal of Medicine, Volume 377, Issue 9, Page 888-890, August 2017.
August 31, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28837144/long-noncoding-rna-xist-expedites-metastasis-and-modulates-epithelial-mesenchymal-transition-in-colorectal-cancer
#15
Dong-Liang Chen, Le-Zong Chen, Yun-Xin Lu, Dong-Sheng Zhang, Zhao-Lei Zeng, Zhi-Zhong Pan, Peng Huang, Feng-Hua Wang, Yu-Hong Li, Huai-Qiang Ju, Rui-Hua Xu
Tumor progression and metastasis is the main cause of death in colorectal cancer (CRC). Long noncoding RNAs (lncRNAs) are critical regulators in various diseases including human cancer. In this study, we found that lncRNA XIST was overexpressed in CRC cell lines and tissues. High expression of lncRNA XIST was associated with adverse overall survival in CRC patients. Knockdown of lncRNA XIST remarkably inhibited CRC cell proliferation, invasion, epithelial-mesenchymal transition (EMT) and CRC stem cell formation in vitro as well as tumor growth and metastasis in vivo...
August 24, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28833104/low-folate-metabolic-stress-reprograms-dna-methylation-activated-sonic-hedgehog-signaling-to-mediate-cancer-stem-cell-like-signatures-and-invasive-tumour-stage-specific-malignancy-of-human-colorectal-cancers
#16
Hsin-Chun Feng, Jhuan-Yu Lin, Shu-Han Hsu, Wen-Yu Lan, Chang-Sheng Kuo, Yu-Feng Tian, Ding-Ping Sun, Rwei-Fen Syu Huang
The mechanistic role of colonic low folate metabolic stress (LFMS) in colorectal cancer (CRC) malignancy development remains unknown. Folate analysis on the 99 paired human CRC tissues localized LFMS to the deep invasive T3/T4 staged tumours with hypo-methylated sonic hedgehog (Shh) promoter region and amplified expressions of Shh ligand and Gli1 effectors, which coincided with deregulated expressions of the epithelial-mesenchymal transition (EMT) mediators. Colonic folate levels of CR were inversely correlated with pluripotent expressions of the SOX2, NANOG and OCT4 markers (P < 0...
August 22, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28827371/strap-promotes-stemness-of-human-colorectal-cancer-via-epigenetic-regulation-of-the-notch-pathway
#17
Lin Jin, Trung Vu, Guandou Yuan, Pran K Datta
NOTCH signaling exerts essential roles in normal and malignant intestinal physiology and the homeostasis of cancer stem-like cells (CSC), but the basis for this latter role remains obscure. The signaling scaffold protein STRAP is upregulated in several cancers where it promotes tumorigenicity and metastasis. Here we report a novel oncogenic function for STRAP in maintaining CSC subpopulations in a heterogeneous mixture by antagonizing formation of the chromatin modifier PRC2 and by epigenetically activating NOTCH signals in human colorectal cancer (CRC)...
August 21, 2017: Cancer Research
https://www.readbyqxmd.com/read/28825595/histone-methyltransferase-setd2-modulates-alternative-splicing-to-inhibit-intestinal-tumorigenesis
#18
Huairui Yuan, Ni Li, Da Fu, Jiale Ren, Jingyi Hui, Junjie Peng, Yongfeng Liu, Tong Qiu, Min Jiang, Qiang Pan, Ying Han, Xiaoming Wang, Qintong Li, Jun Qin
The histone H3K36 methyltransferase SETD2 is frequently mutated or deleted in a variety of human tumors. Nevertheless, the role of SETD2 loss in oncogenesis remains largely undefined. Here, we found that SETD2 counteracts Wnt signaling and its inactivation promotes intestinal tumorigenesis in mouse models of colorectal cancer (CRC). SETD2 was not required for intestinal homeostasis under steady state; however, upon irradiation, genetic inactivation of Setd2 in mouse intestinal epithelium facilitated the self-renewal of intestinal stem/progenitor cells as well as tissue regeneration...
September 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28807224/mesua-ferrea-stem-bark-extract-induces-apoptosis-and-inhibits-metastasis-in-human-colorectal-carcinoma-hct-116-cells-through-modulation-of-multiple-cell-signalling-pathways
#19
Muhammad Asif, Armaghan Shafaei, Aman Shah Abdul Majid, Mohammed Oday Ezzat, Saad S Dahham, Mohamed B Khadeer Ahamed, Chern Ein Oon, Amin Malik Shah Abdul Majid
Considering the great potential of natural products as anticancer agents, the present study was designed to explore the molecular mechanisms responsible for anticancer activities of Mesua ferrea stem bark extract against human colorectal carcinoma. Based on MTT assay results, bioactive sub-fraction (SF-3) was selected for further studies using HCT 116 cells. Repeated column chromatography resulted in isolation of less active α-amyrin from SF-3, which was identified and characterized by GC-MS and HPLC methods...
July 2017: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/28791382/potential-role-of-zeb1-as-a-dna-repair-regulator-in-colorectal-cancer-cells-revealed-by-cancer-associated-promoter-profiling
#20
Miao Wang, Su-Fei He, Lei-Lei Liu, Xiao-Xia Sun, Fan Yang, Qian Ge, Wei-Kang Wong, Jing-Yan Meng
Besides being a key contributor to epithelial‑to‑mesenchymal transition (EMT) activation and stemness maintenance, zinc finger E-box binding homeobox 1 (ZEB1) is also a crucial inducer of chemoresistance and radioresistance. Unlike the clear mechanism that mediates its effect on EMT and dedifferentiation, the mechanism of how ZEB1 promotes chemo- and radio-resistance remains to be elucidated. It has been previously reported that ZEB1 promotes DNA double-strand break clearance by enhancing the deubiquitylating activity of ubiquitin-specific peptidase (USP)7 on checkpoint kinase 1, which is an important step during DNA repair...
August 8, 2017: Oncology Reports
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