scholarly journals Genomic determinants of protein abundance variation in colorectal cancer cells

2016 ◽  
Author(s):  
Theodoros I. Roumeliotis ◽  
Steven Paul Williams ◽  
Emanuel Gonçalves ◽  
Fatemeh Zamanzad Ghavidel ◽  
Nanne Aben ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Protein Interactions ◽  
Metal Ion ◽  
Genomic Variation ◽  
List Type ◽  
Integrative View ◽  
Colorectal Cancer Cells ◽  
Chromatin Modifiers

SummaryAssessing the extent to which genomic alterations compromise the integrity of the proteome is fundamental in identifying the mechanisms that shape cancer heterogeneity. We have used isobaric labelling and tribrid mass spectrometry to characterize the proteomic landscapes of 50 colorectal cancer cell lines and to decipher the relationships between genomic and proteomic variation. The robust quantification of 12,000 proteins and 27,000 phosphopeptides revealed how protein symbiosis translates to a co-variome which is subjected to a hierarchical order and exposes the collateral effects of somatic mutations on protein complexes. Targeted depletion of key chromatin modifiers confirmed the transmission of variation and the directionality as characteristics of protein interactions. Protein level variation was leveraged to build drug response predictive models towards a better understanding of pharmacoproteomic interactions in colorectal cancer. Overall, we provide a deep integrative view of the molecular structure underlying the variation of colorectal cancer cells.HighlightsThe cancer cell functional “co-variome” is a strong attribute of the proteome.Mutations can have a direct impact on protein levels of chromatin modifiers.Transmission of genomic variation is a characteristic of protein interactions.Pharmacoproteomic models are strong predictors of response to DNA damaging agents.AbbreviationsCOREADColorectal AdenocarcinomaIMACImmobilized Metal ion Affinity ChromatographyROCReceiver Operating CharacteristicAUCArea Under the CurveWGCNAWeighted Correlation Network AnalysisCNACopy Number AlterationSOMSelf-Organizing MapQTLQuantitative Trait LociMSIMicrosatellite InstabilityCPSColorectal Proteomic Subtypes

scholarly journals Pals1 prevents Rac1-dependent colorectal cancer cell metastasis by inhibiting Arf6

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Simona Mareike Lüttgenau ◽  
Christin Emming ◽  
Thomas Wagner ◽  
Julia Harms ◽  
Justine Guske ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Scaffolding Protein ◽  
Migration And Invasion ◽  
Tight Junction Formation ◽  
Cell Metastasis ◽  
Colorectal Cancer Cells

AbstractLoss of apical-basal polarity and downregulation of cell-cell contacts is a critical step during the pathogenesis of cancer. Both processes are regulated by the scaffolding protein Pals1, however, it is unclear whether the expression of Pals1 is affected in cancer cells and whether Pals1 is implicated in the pathogenesis of the disease.Using mRNA expression data and immunostainings of cancer specimen, we show that Pals1 is frequently downregulated in colorectal cancer, correlating with poorer survival of patients. We further found that Pals1 prevents cancer cell metastasis by controlling Rac1-dependent cell migration through inhibition of Arf6, which is independent of the canonical binding partners of Pals1. Loss of Pals1 in colorectal cancer cells results in increased Arf6 and Rac1 activity, enhanced cell migration and invasion in vitro and increased metastasis of transplanted tumor cells in mice. Thus, our data reveal a new function of Pals1 as a key inhibitor of cell migration and metastasis of colorectal cancer cells. Notably, this new function is independent of the known role of Pals1 in tight junction formation and apical-basal polarity.

scholarly journals Gold nanoparticles conjugated with anti-CD133 monoclonal antibody and 5-fluorouracil chemotherapeutic agent as nanocarriers for cancer cell targeting

RSC Advances ◽  
2021 ◽  
Vol 11 (26) ◽  
pp. 16131-16141
Author(s):  
Manali Haniti Mohd-Zahid ◽  
Siti Nadiah Zulkifli ◽  
Che Azurahanim Che Abdullah ◽  
JitKang Lim ◽  
Sharida Fakurazi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibody ◽  
Gold Nanoparticles ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Chemotherapeutic Agent ◽  
Cell Targeting ◽  
Specific Targeting ◽  
Colorectal Cancer Cells ◽  
Cancer Cell Targeting

5-FU-PEGylated AuNPs-CD133 is designed to improve specific targeting of 5-FU against colorectal cancer cells which abundantly express CD133.

scholarly journals Comparative proteomics—network analysis of proteins responsible for ursolic acid–induced cytotoxicity in colorectal cancer cells

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769501 ◽  
Author(s):  
Qiaoyan Cai ◽  
Jing Lin ◽  
Ling Zhang ◽  
Jiumao Lin ◽  
Lili Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Ursolic Acid ◽  
Protein Interactions ◽  
Direct Interaction ◽  
Interaction Network ◽  
Two Dimensional Gel Electrophoresis ◽  
Cellular Targets ◽  
Protein Protein Interaction ◽  
Colorectal Cancer Cells

Ursolic acid is a key active compound present in many medicinal herbs that have been widely used in traditional Chinese medicine for the clinical treatment of various cancers. However, the precise mechanisms of its antitumor activity have been poorly understood. To identify the cellular targets of ursolic acid, two-dimensional gel electrophoresis combined with mass spectrometry was performed in this study, which identified 15 proteins with significantly altered levels in protein expression. This demonstrated that ursolic acid–induced cytotoxicity in colorectal cancer cells involves dysregulation in protein folding, signal transduction, cell proliferation, cell cycle, and apoptosis. Corresponding protein regulation was also confirmed by Western blotting. Furthermore, the study of functional association between these 15 proteins revealed that 10 were closely related in a protein–protein interaction network, whereby the proteins either had a direct interaction with each other or were associated via only one intermediary protein. In this instance, the ATP5B/CALR/HSP90B1/HSPB1/HSPD1-signaling network was revealed as the predominant target which was associated with the majority of the observed protein–protein interactions. As a result, the identified targets may be useful in explaining the anticancer mechanisms of ursolic acid and as potential targets for colorectal cancer therapy.

scholarly journals An Integrated Bioinformatics Analysis Repurposes an Antihelminthic Drug Niclosamide for Treating HMGA2-Overexpressing Human Colorectal Cancer

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1482 ◽  
Author(s):  
Leung ◽  
Chou ◽  
Huang ◽  
Yang
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Gene Signature ◽  
Cancer Cell Lines ◽  
Colorectal Cancer Cell ◽  
Sequencing Analysis ◽  
Colorectal Cancer Cells ◽  
Colorectal Cancer Cell Lines

Aberrant overexpression of high mobility group AT-hook 2 (HMGA2) is frequently found in cancers and HMGA2 has been considered an anticancer therapeutic target. In this study, a pan-cancer genomics survey based on Cancer Cell Line Encyclopedia (CCLE) and The Cancer Genome Atlas (TCGA) data indicated that HMGA2 was mainly overexpressed in gastrointestinal cancers including colorectal cancer. Intriguingly, HMGA2 overexpression had no prognostic impacts on cancer patients’ overall and disease-free survivals. In addition, HMGA2-overexpressing colorectal cancer cell lines did not display higher susceptibility to a previously identified HMGA2 inhibitor (netroposin). By microarray profiling of HMGA2-driven gene signature and subsequent Connectivity Map (CMap) database mining, we identified that S100 calcium-binding protein A4 (S100A4) may be a druggable vulnerability for HMGA2-overexpressing colorectal cancer. A repurposing S100A4 inhibitor, niclosamide, was found to reverse the HMGA2-driven gene signature both in colorectal cancer cell lines and patients’ tissues. In vitro and in vivo experiments validated that HMGA2-overexpressing colorectal cancer cells were more sensitive to niclosamide. However, inhibition of S100A4 by siRNAs and other inhibitors was not sufficient to exert effects like niclosamide. Further RNA sequencing analysis identified that niclosamide inhibited more cell-cycle-related gene expression in HMGA2-overexpressing colorectal cancer cells, which may explain its selective anticancer effect. Together, our study repurposes an anthelminthic drug niclosamide for treating HMGA2-overexpression colorectal cancer.

scholarly journals A Low-Cost and Portable Smart Instrumentation for Detecting Colorectal Cancer Cells

2019 ◽  
Vol 9 (17) ◽  
pp. 3510 ◽  
Author(s):  
Mohammad Wajih Alam ◽  
Khan A. Wahid ◽  
Md. Fahmid Islam ◽  
Wendy Bernhard ◽  
Clarence R. Geyer ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Mammalian Cells ◽  
Imaging System ◽  
Low Cost ◽  
Colorectal Cancer Cell ◽  
Colorectal Cancer Cell Line ◽  
Visible Range ◽  
Colorectal Cancer Cells

Fluorescence imaging is a well-known method for monitoring fluorescence emitted from the subject of interest and provides important insights about cell dynamics and molecules in mammalian cells. Currently, many solutions exist for measuring fluorescence, but the application methods are complex and the costs are high. This paper describes the design and development of a low-cost, smart and portable fluorimeter for the detection of colorectal cancer cell expressing IRFP702. A flashlight is used as a light source, which emits light in the visible range and acts as an excitation source, while a photodiode is used as a detector. It also uses a longpass filter to only allow the wavelength of interest to pass from the cultured cell. It eliminates the need of both the dichroic mirror and excitation filter, which makes the developed device low cost, compact and portable as well as lightweight. The custom-built sample chamber is black in color to minimize interference and is printed with a 3D printer to accommodate the detector circuitry. An established colorectal cancer cell line (human colorectal carcinoma (HCT116)) was cultured in the laboratory environment. A near-infrared fluorescent protein IRFP702 was expressed in the colorectal cancer cells that were used to test the proof-of-concept. The fluorescent cancer cells were first tested with a commercial imaging system (Odyssey® CLx) and then with the developed prototype to validate the result in a preclinical setting. The developed fluorimeter is versatile as it can also be used to detect multiple types of cancer cells by simply replacing the filters based on the fluorophore.

Tu1668 Highly Metastatic Murine Colorectal Cancer Cells Share Transcriptome Identity Indicative of Cancer Cell Fusion With Macrophages

2014 ◽  
Vol 146 (5) ◽  
pp. S-814
Author(s):  
Charles E. Gast ◽  
Alain Silk ◽  
Mark Schmidt ◽  
Lara Riegler ◽  
Chris Harrington ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cell Fusion ◽  
Cancer Cell ◽  
Colorectal Cancer Cells

scholarly journals Energy Metabolic Plasticity of Colorectal Cancer Cells as a Determinant of Tumor Growth and Metastasis

2021 ◽  
Vol 11 ◽  
Author(s):  
Leenu Reinsalu ◽  
Marju Puurand ◽  
Vladimir Chekulayev ◽  
Sten Miller ◽  
Igor Shevchuk ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Colorectal Carcinogenesis ◽  
Voltage Dependent Anion Channel ◽  
Metabolic Plasticity ◽  
Colorectal Cancer Cells ◽  
Functional Features

Metabolic plasticity is the ability of the cell to adjust its metabolism to changes in environmental conditions. Increased metabolic plasticity is a defining characteristic of cancer cells, which gives them the advantage of survival and a higher proliferative capacity. Here we review some functional features of metabolic plasticity of colorectal cancer cells (CRC). Metabolic plasticity is characterized by changes in adenine nucleotide transport across the outer mitochondrial membrane. Voltage-dependent anion channel (VDAC) is the main protein involved in the transport of adenine nucleotides, and its regulation is impaired in CRC cells. Apparent affinity for ADP is a functional parameter that characterizes VDAC permeability and provides an integrated assessment of cell metabolic state. VDAC permeability can be adjusted via its interactions with other proteins, such as hexokinase and tubulin. Also, the redox conditions inside a cancer cell may alter VDAC function, resulting in enhanced metabolic plasticity. In addition, a cancer cell shows reprogrammed energy transfer circuits such as adenylate kinase (AK) and creatine kinase (CK) pathway. Knowledge of the mechanism of metabolic plasticity will improve our understanding of colorectal carcinogenesis.

scholarly journals Interleukin Receptor Antagonist Inhibits Matastatic Potential by Down-Regulating CXCL12/CXCR4 Signaling Axis in Colorectal Cancer

2021 ◽  
Author(s):  
Jiachi Ma ◽  
Wanqing Liang ◽  
Yaosheng Qiang ◽  
Lei Li ◽  
Jun Du ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Stromal Cells ◽  
Metastatic Potential ◽  
Colorectal Cancer Cell ◽  
Colorectal Cancer Cells ◽  
Ht 29 ◽  
High Liver

Abstract Background: The aim of this study was to investigate the co-operative role of CXCR4/ CXCL12 axis and IL-1Ra in metastatic processes mechanism by interactions between colorectal cancer cells and stromal cells in their microenvironment. Methods: Expression of IL-1a, CXCL12 and CXCR4 mRNA and proteins were determined by RT-PCR and Western blot. The effect of secreted level of CXCL12 by IL-1Ra on fibroblasts was measured by ELISA. CXCL12 regulate metastatic potential of colorectal cancer was evaluated by proliferation, invasion and angiogenesis assays, respectively, in which invasion and angiogenesis assays used an in vitro system consisting of co-cultured colorectal cells and stromal cells. Results: IL-1a was expressed in high liver metastatic colorectal cancer cell lines (HT-29 and WiDr). The colorectal cancer cell-derived IL-1a and rIL-1a significantly promoted CXCL12 expression by fibroblasts, and this enhancing effect can be significantly inhibited by IL-1Ra (P<0.01). CXCL12 not only enhanced the migration and proliferation of human umbilical vein endothelial cells (HUVECs), but also significantly enhanced angiogenesis (P<0.01). Furthermore, the high liver-metastatic colorectal cancer cell line (HT-29), which secretes IL-1a, significantly enhanced angiogenesis compared to the low liver-metastatic cell line (CaCo-2), which does not produce IL-1a (P<0.01). On the contrary, IL-1Ra can significantly inhibit migration, proliferation and angiogenesis (P<0.01). Conclusion: Autocrine IL-1a and paracrine CXCL12 co-enhances the metastatic potential of colorectal cancer cells; IL-1Ra can inhibit the metastatic potential of colorectal cancer cells via decrease IL-1a/CXCR4/CXCL12 signaling pathways.

scholarly journals Xanthium strumarium Fruit Extract Inhibits ATG4B and Diminishes the Proliferation and Metastatic Characteristics of Colorectal Cancer Cells

Toxins ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 313 ◽  
Author(s):  
Hsueh-Wei Chang ◽  
Pei-Feng Liu ◽  
Wei-Lun Tsai ◽  
Wan-Hsiang Hu ◽  
Yu-Chang Hu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Plant Extracts ◽  
Migration And Invasion ◽  
Xanthium Strumarium ◽  
Autophagic Flux ◽  
Tribulus Terrestris ◽  
Fruit Extract ◽  
Colorectal Cancer Cells

Autophagy is an evolutionarily conserved pathway to degrade damaged proteins and organelles for subsequent recycling in cells during times of nutrient deprivation. This process plays an important role in tumor development and progression, allowing cancer cells to survive in nutrient-poor environments. The plant kingdom provides a powerful source for new drug development to treat cancer. Several plant extracts induce autophagy in cancer cells. However, little is known about the role of plant extracts in autophagy inhibition, particularly autophagy-related (ATG) proteins. In this study, we employed S-tagged gamma-aminobutyric acid receptor associated protein like 2 (GABARAPL2) as a reporter to screen 48 plant extracts for their effects on the activity of autophagy protease ATG4B. Xanthium strumarium and Tribulus terrestris fruit extracts were validated as potential ATG4B inhibitors by another reporter substrate MAP1LC3B-PLA2. The inhibitory effects of the extracts on cellular ATG4B and autophagic flux were further confirmed. Moreover, the plant extracts significantly reduced colorectal cancer cell viability and sensitized cancer cells to starvation conditions. The fruit extract of X. strumarium consistently diminished cancer cell migration and invasion. Taken together, the results showed that the fruit of X. strumarium may have an active ingredient to inhibit ATG4B and suppress the proliferation and metastatic characteristics of colorectal cancer cells.

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