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https://www.readbyqxmd.com/read/29330293/differential-regulation-of-let-7-by-lin28b-isoform-specific-functions
#1
Rei Mizuno, Priya Chatterji, Sarah F Andres, Kathryn E Hamilton, Lauren Simon, Shawn W Foley, Arjun N Jeganathan, Brian D Gregory, Blair B Madison, Anil K Rustgi
The RNA binding protein LIN28B plays an important role in development, stem cell biology and tumorigenesis. LIN28B has two isoforms: the LIN28B-long and -short isoforms. Although studies have revealed the functions of the LIN28B-long isoform in tumorigenesis, the role of the LIN28B-short isoform remains unclear and represents a major gap in the field. The LIN28B-long and -short isoforms are expressed in a subset of human colorectal cancers (CRCs) and adjacent normal colonic mucosa, respectively. To elucidate the functional and mechanistic aspects of these isoforms, CRC cells (Caco-2 and LoVo) were generated to either express no LIN28B or the -short or -long isoform...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29329541/a-role-for-endothelial-nitric-oxide-synthase-in-intestinal-stem-cell-proliferation-and-mesenchymal-colorectal-cancer
#2
Jon Peñarando, Laura M López-Sánchez, Rafael Mena, Silvia Guil-Luna, Francisco Conde, Vanessa Hernández, Marta Toledano, Victoria Gudiño, Michela Raponi, Caroline Billard, Carlos Villar, César Díaz, José Gómez-Barbadillo, Juan De la Haba-Rodríguez, Kevin Myant, Enrique Aranda, Antonio Rodríguez-Ariza
BACKGROUND: Nitric oxide (NO) has been highlighted as an important agent in cancer-related events. Although the inducible nitric oxide synthase (iNOS) isoform has received most attention, recent studies in the literature indicate that the endothelial isoenzyme (eNOS) can also modulate different tumor processes including resistance, angiogenesis, invasion, and metastasis. However, the role of eNOS in cancer stem cell (CSC) biology and mesenchymal tumors is unknown. RESULTS: Here, we show that eNOS was significantly upregulated in VilCre ERT2 Apc fl/+ and VilCre ERT2 Apc fl/fl mouse intestinal tissue, with intense immunostaining in hyperproliferative crypts...
January 10, 2018: BMC Biology
https://www.readbyqxmd.com/read/29328371/cd133-expression-predicts-post-operative-recurrence-in-patients-with-colon-cancer-with-peritoneal-metastasis
#3
Hiroshi Nagata, Soichiro Ishihara, Junko Kishikawa, Hirofumi Sonoda, Koji Murono, Shigenobu Emoto, Manabu Kaneko, Kazuhito Sasaki, Kensuke Otani, Takeshi Nishikawa, Toshiaki Tanaka, Tomomichi Kiyomatsu, Keisuke Hata, Kazushige Kawai, Hiroaki Nozawa
Despite extensive research on cancer stem cells in colorectal cancer, the impact of stem cell markers on patient survival remains unclear, particularly in those with distant metastasis. In this study, we focused on colon cancer with peritoneal metastasis and investigated the association between the expression of CD133, aldehyde dehydrogenase-1 (ALDH1) and leucine-rich repeating G-protein coupled receptor-5 (Lgr5), and disease prognosis. Putative stem cell marker expression was immunohistochemically evaluated in samples from 142 primary tumours and 75 peritoneal nodules...
January 8, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29323154/effects-of-metformin-on-colorectal-cancer-stem-cells-depend-on-alterations-in-glutamine-metabolism
#4
Jae Hyun Kim, Kyoung Jin Lee, Yoojeong Seo, Ji-Hee Kwon, Jae Pil Yoon, Jo Yeon Kang, Hyun Jung Lee, Soo Jung Park, Sung Pil Hong, Jae Hee Cheon, Won Ho Kim, Tae Ii Kim
Metformin has been known to suppress cancer stem cells (CSCs) in some cancers. However, the differential effects of metformin on CSCs and their mechanisms have not been reported. Herein, metformin induced pAMPK activation and pS6 suppression in metformin-sensitive (HT29) cells, but not in metformin-resistant (SW620) cells. The oxygen consumption rate was higher in HT29 cells than in SW620 cells and showed a prominent decrease after metformin treatment in HT29 cells. In glutamine-depleted medium, but not in low-glucose medium, SW620 cells became sensitive to the CSC-suppressing effect of metformin...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29316729/wnt-rspo-and-hippo-signalling-in-the-intestine-and-intestinal-stem-cells
#5
REVIEW
Vitezslav Kriz, Vladimir Korinek
In this review, we address aspects of Wnt, R-Spondin (RSPO) and Hippo signalling, in both healthy and transformed intestinal epithelium. In intestinal stem cells (ISCs), the Wnt pathway is essential for intestinal crypt formation and renewal, whereas RSPO-mediated signalling mainly affects ISC numbers. In human colorectal cancer (CRC), aberrant Wnt signalling is the driving mechanism initiating this type of neoplasia. The signalling role of the RSPO-binding transmembrane proteins, the leucine-rich-repeat-containing G-protein-coupled receptors (LGRs), is possibly more pleiotropic and not only limited to the enhancement of Wnt signalling...
January 8, 2018: Genes
https://www.readbyqxmd.com/read/29313727/polymethoxylated-flavones-from-orange-peels-inhibit-cell-proliferation-in-a-3d-cell-model-of-human-colorectal-cancer
#6
Inês Silva, Marta F Estrada, Carolina V Pereira, Andreia Bento da Silva, Maria R Bronze, Paula M Alves, Catarina M M Duarte, Catarina Brito, Ana Teresa Serra
Polymethoxylated flavones (PMFs) have been recognized to inhibit colorectal cancer proliferation through various mechanisms, however most of these studies have been performed on cells grown as monolayers that present limitations in mimicking the 3D tumor architecture and microenvironment. The main aim of this study was to investigate the anticancer potential of an orange peel extract (OPE) enriched in PMFs in a 3D cell model of colorectal cancer. The OPE was developed by supercritical fluid extraction and the anticancer effect was evaluated in HT29 spheroids cultures in a stirred-tank based system...
January 9, 2018: Nutrition and Cancer
https://www.readbyqxmd.com/read/29312609/ascl2-activation-by-yap1-klf5-ensures-the-self-renewability-of-colon-cancer-progenitor-cells
#7
Xiaolong Wei, Jun Ye, Yangyang Shang, Haoyuan Chen, Shanxi Liu, Li Liu, Rongquan Wang
Achaete scute-like 2 (Ascl2) is the Wnt signaling target, its regulation by other signaling is undefined. Now we demonstrated that CD133+/CD44+ cell population from HT-29 or Caco-2 cells exhibited cancer stem cell (CSC) properties with highly expressed Ascl2, which is related to the Hippo signaling pathway. YAP1 interference in CD133+/CD44+ HT-29 or Caco-2 cells reduced their proliferation, colony-forming ability and tumorsphere formation in vitro and inhibited the 'stemness'-associated genes and Ascl2 expression...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29312533/loss-of-pacs-2-delays-regeneration-in-dss-induced-colitis-but-does-not-affect-the-apcmin-model-of-colorectal-cancer
#8
Sarah L Dombernowsky, Jeanette Schwarz, Jacob Samsøe-Petersen, Reidar Albrechtsen, Kim B Jensen, Gary Thomas, Marie Kveiborg
PACS-2 is a multifunctional sorting protein that mediates cell homeostasis. We recently identified PACS-2 in a functional genome-wide siRNA screen for novel regulators of the metalloproteinase ADAM17, the main sheddase for ligands of the ErbB receptor family. Of note, we showed that Pacs2-/- mice have significantly reduced EGFR activity and proliferative index in the intestinal epithelium. As EGFR signaling is highly mitogenic for intestinal epithelial stem cells, and plays essential roles in intestinal epithelial regeneration and tumor development, we have now examined the role of PACS-2 in these processes...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29302705/multi-scale-modeling-of-apc-and-formula-see-text-catenin-regulation-in-the-human-colonic-crypt
#9
Brooks Emerick, Gilberto Schleiniger, Bruce M Boman
Stem cell renewal and differentiation in the human colonic crypt are linked to the [Formula: see text]-catenin pathway. The spatial balance of Wnt factors in proliferative cells within the crypt maintain an appropriate level of cellular reproduction needed for normal crypt homeostasis. Mutational events at the gene level are responsible for deregulating the balance of Wnt factors along the crypt, causing an overpopulation of proliferative cells, a loss of structure of the crypt domain, and the initiation of colorectal carcinomas...
January 4, 2018: Journal of Mathematical Biology
https://www.readbyqxmd.com/read/29299179/lncrnas-and-their-role-in-cancer-stem-cells
#10
REVIEW
Shusen Chen, Jiamin Zhu, Feng Wang, Zhifeng Guan, Yangyang Ge, Xi Yang, Jing Cai
Cancer stem cells (CSCs) play a vital role in the formation of tumors and have been studied as a target of anticancer therapy. Long non-coding RNAs (lncRNAs) are important in the genesis and progression of cancer. Various lncRNAs, such as ROR, HOTAIR, H19, UCA1, and ARSR, are involved in cancer stemness. These lncRNAs could regulate the expression of CSC-related transcriptional factors, such as SOX2, OCT4, and NANOG, in colorectal, prostate, bladder, breast, liver, and other cancer types. In this work, we review the progress of lncRNAs and cancer stem cells and discuss the potential signal pathways of lncRNAs in cancer stemness...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296212/small-sized-colorectal-cancer-cells-harbor-metastatic-tumor-initiating-cells
#11
Lei Mu, Kaiyu Huang, Yibing Hu, Chang Yan, Xiaolan Li, Deding Tao, Jianping Gong, Jichao Qin
Colorectal cancer (CRC) is heterogeneous and contains different-sized cells. Recent studies have shown that tumor-initiating cells (TICs) are involved in cancer initiation, recurrence and metastasis. However, connections between cancer cell size and stem-like properties are largely unknown. Here we purified large- and small-sized CRC cells by fluorescence-activated cell sorting (FACS) based on forward scatter (FSC), and demonstrated that small CRC cells possess higher holoclone- and sphere-forming capacity in vitro, tumor-initiating capacity in vivo and form more lung metastases compared with large CRC cells...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29281831/degree-of-tissue-differentiation-dictates-susceptibility-to-braf-driven-colorectal-cancer
#12
Kevin Tong, Oscar Pellón-Cárdenas, Veerin R Sirihorachai, Bailey N Warder, Om A Kothari, Ansu O Perekatt, Emily E Fokas, Robert L Fullem, Anbo Zhou, Joshua K Thackray, Hiep Tran, Lanjing Zhang, Jinchuan Xing, Michael P Verzi
Oncogenic mutations in BRAF are believed to initiate serrated colorectal cancers; however, the mechanisms of BRAF-driven colon cancer are unclear. We find that oncogenic BRAF paradoxically suppresses stem cell renewal and instead promotes differentiation. Correspondingly, tumor formation is inefficient in BRAF-driven mouse models of colon cancer. By reducing levels of differentiation via genetic manipulation of either of two distinct differentiation-promoting factors (Smad4 or Cdx2), stem cell activity is restored in BRAFV600E intestines, and the oncogenic capacity of BRAFV600E is amplified...
December 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/29278988/cytotoxic-activity-of-the-bioactive-principles-from-ficus-burtt-davyi
#13
Olumuyiwa O Ogunlaja, Roshila Moodley, Moganavelli Singh, Himansu Baijnath, Sreekanth B Jonnalagadda
Ficus burtt-davyi (Moraceae) is a medicinal plant species indigenous to Southern Africa. In this study, a phytochemical and cytotoxic investigation on F. burtt-davyi was conducted to evaluate its ethno-medicinal use. The phytochemical study of the fruits yielded triterpenoids (lupeol and α-amyrin). The cytotoxic evaluation was done on the methanolic extracts and selected compounds, lupeol, α-amyrin, lupeol acetate and (+)-catechin isolated from F. burtt-davyi stem bark and fruits. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay was carried out against two human cancer cell lines, breast adenocarcinoma (MCF-7) and colorectal adenocarcinoma (Caco-2), and normal human embryonic kidney cells (HEK293)...
December 26, 2017: Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes
https://www.readbyqxmd.com/read/29250169/therapeutic-strategies-against-cancer-stem-cells-in-human-colorectal-cancer
#14
Magdalena Szaryńska, Agata Olejniczak, Jarosław Kobiela, Piotr Spychalski, Zbigniew Kmieć
Colorectal cancer (CRC) is the third most frequent malignancy and represents the fourth most common cause of cancer-associated mortalities in the world. Despite many advances in the treatment of CRC, the 5-year survival rate of patients with CRC remains unsatisfactory due to tumor recurrence and metastases. Recently, cancer stem cells (CSCs), have been suggested to be responsible for the initiation and relapse of the disease, and have been identified in CRC. Due to their basic biological features, which include self-renewal and pluripotency, CSCs may be novel therapeutic targets for CRC and other cancer types...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29241656/adipose-derived-stem-cells-decrease-pain-in-a-rat-model-of-oxaliplatin-induced-neuropathy-role-of-vegf-a-modulation
#15
Lorenzo Di Cesare Mannelli, Barbara Tenci, Laura Micheli, Alessia Vona, Francesca Corti, Matteo Zanardelli, Andrea Lapucci, Ann Maria Clemente, Paola Failli, Carla Ghelardini
Oxaliplatin therapy of colorectal cancer induces a dose-dependent neuropathic syndrome in 50% of patients. Pharmacological treatments may offer limited relief; scientific efforts are needed for new therapeutic approaches. Therefore we evaluated in a preclinical setting the pain relieving properties of mesenchymal stem cells and its secretome. Rat adipose stem cells (rASCs) were administered in a rat model of oxaliplatin-induced neuropathy. A single intravenous injection of rASCs reduced oxaliplatin-dependent mechanical hypersensitivity to noxious and non-noxious stimuli taking effect 1 h after administration, peaking 6 h thereafter and lasting 5 days...
December 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29228716/sox2-modulates-motility-and-enhances-progression-of-colorectal-cancer-via-the-rho-rock-signaling-pathway
#16
Junheng Zheng, Lixiao Xu, Yubin Pan, Shuyi Yu, Hongbo Wang, Derek Kennedy, Yan Zhang
Sox2 (Sry-box2) is essential for a variety of stem cells and is also expressed in colorectal cancer (CRC). However, the underlying mechanism by which Sox2 enhances CRC progression remains unclear. In the present study, we show that elevated Sox2 expression is significantly correlated with poor clinical prognosis. CRC is phenotypically heterogeneous, and harbors several subtypes of cancer cells. Elevated Sox2 expression was always detected in rounded-shape cells, which co-located to poorly differentiated regions, the invasive frontier and metastatic lesions...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29226326/retreg1-fam134b-a-new-player-in-human-diseases-15-years-after-the-discovery-in-cancer
#17
REVIEW
Farhadul Islam, Vinod Gopalan, Alfred King-Yin Lam
FAM134B (family with sequence similarity 134, member B) / RETREG1 and its functional roles are relatively new in human diseases. This review aimed to summarize various functions of FAM134B since our first discovery of the gene in 2001. The protein encoded by FAM134B is a reticulophagy receptor that regulates turnover of the endoplasmic reticulum (ER) by selective phagocytosis. Absence or non-functional expression of FAM134B protein impairs ER-turnover and thereby is involved in the pathogenesis of some human diseases...
December 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29218591/model-based-phenotypic-signatures-governing-the-dynamics-of-the-stem-and-semi-differentiated-cell-populations-in-dysplastic-colonic-crypts
#18
Svetoslav Nikolov, Guido Santos, Olaf Wolkenhauer, Julio Vera
Mathematical modeling of cell differentiated in colonic crypts can contribute to a better understanding of basic mechanisms underlying colonic tissue organization, but also its deregulation during carcinogenesis and tumor progression. Here, we combined bifurcation analysis to assess the effect that time delay has in the complex interplay of stem cells and semi-differentiated cells at the niche of colonic crypts, and systematic model perturbation and simulation to find model-based phenotypes linked to cancer progression...
December 7, 2017: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/29207577/replication-stress-in-colorectal-cancer-stem-cells
#19
EDITORIAL
Gwenola Manic, Ruggero De Maria, Ilio Vitale
No abstract text is available yet for this article.
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207035/in-vitro-characterization-of-spheres-derived-from-colorectal-cancer-cell-lines
#20
Agata Olejniczak, Magdalena Szaryńska, Zbigniew Kmieć
Spherical cultures (SCs) can be regarded in cancer research as a link between in vitro investigations on cancer lines and in vivo studies of tumor development. SCs are believed to mimic tumor architecture and to be enriched in cancer stem cell-like cells (CSC-like cells). In the present study we characterized colonospheres derived from colorectal cancer (CRC) cell lines, and we confirmed the ability of HCT116 and HT29 cell lines to form spheres within serum-free medium, however, the detailed analysis presented the major differences concerning their characteristics including morphology, phenotype, proliferative potential, distribution in the cell cycle phases and spherogenicity...
November 16, 2017: International Journal of Oncology
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