scholarly journals Interaction between Tumor-Associated Dendritic Cells and Colon Cancer Cells Contributes to Tumor Progression via CXCL1

2018 ◽  
Vol 19 (8) ◽  
pp. 2427 ◽  
Author(s):  
Ya-Ling Hsu ◽  
Yi-Jen Chen ◽  
Wei-An Chang ◽  
Shu-Fang Jian ◽  
Hsiao-Li Fan ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Dendritic Cells ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Critical Factor ◽  
Prognostic Impact ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
Cxcl1 Expression

Crosstalk of a tumor with its microenvironment is a critical factor contributing to cancer development. This study investigates the soluble factors released by tumor-associated dendritic cells (TADCs) responsible for increasing cancer stem cell (CSC) properties, cell mobility, and epithelial-to-mesenchymal transition (EMT). Dendritic cells (DCs) of colon cancer patients were collected for phenotype and CXCL1 expression by flow cytometry and Luminex assays. The transcriptome of CXCL1-treated cancer cells was established by next generation sequencing. Inflammatory chemokine CXCL1, present in large amounts in DCs isolated from colon cancer patients, and SW620-conditioned TADCs, enhance CSC characteristics in cancer, supported by enhanced anchorage-independent growth, CD133 expression and aldehyde dehydrogenase activity. Additionally, CXCL1 increases the metastatic ability of a cancer by enhancing cell migration, matrix metalloproteinase-7 expression and EMT. The enhanced CXCL1 expression in DCs is also noted in mice transplanted with colon cancer cells. Transcriptome analysis of CXCL1-treated SW620 cells indicates that CXCL1 increases potential oncogene expression in colon cancer, including PTHLH, TYRP1, FOXO1, TCF4 and ZNF880. Concurrently, CXCL1 displays a specific microRNA (miR) upregulated by the prototypical colon cancer onco-miR miR-105. Analysis of publicly available data reveals CXCL1-driven oncogenes and miR-105 have a negative prognostic impact on the outcome of colon cancer. This study indicates a new mechanism by which the colon cancer milieu exploits DC plasticity to support cancer progression.

scholarly journals Absence of the Tks4 Scaffold Protein Induces Epithelial-Mesenchymal Transition-Like Changes in Human Colon Cancer Cells

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1343 ◽  
Author(s):  
Szeder ◽  
Tárnoki-Zách ◽  
Lakatos ◽  
Vas ◽  
Kudlik ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Transcription Factors ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Cell Attachment ◽  
Scaffold Protein ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Mesenchymal Transition

Epithelial to mesenchymal transition (EMT) is a multipurpose process involved in wound healing, development, and certain pathological processes, such as metastasis formation. The Tks4 scaffold protein has been implicated in cancer progression; however, its role in oncogenesis is not well defined. In this study, the function of Tks4 was investigated in HCT116 colon cancer cells by knocking the protein out using the CRISPR/Cas9 system. Surprisingly, the absence of Tks4 induced significant changes in cell morphology, motility, adhesion and expression, and localization of E-cadherin, which are all considered as hallmarks of EMT. In agreement with these findings, the marked appearance of fibronectin, a marker of the mesenchymal phenotype, was also observed in Tks4-KO cells. Analysis of the expression of well-known EMT transcription factors revealed that Snail2 was strongly overexpressed in cells lacking Tks4. Tks4-KO cells showed increased motility and decreased cell–cell attachment. Collagen matrix invasion assays demonstrated the abundance of invasive solitary cells. Finally, the reintroduction of Tks4 protein in the Tks4-KO cells restored the expression levels of relevant key transcription factors, suggesting that the Tks4 scaffold protein has a specific and novel role in EMT regulation and cancer progression.

scholarly journals Elevated ATGL in colon cancer cells and cancer stem cells promotes metabolic and tumorigenic reprogramming reinforced by obesity

Oncogenesis ◽  
2021 ◽  
Vol 10 (11) ◽  
Author(s):  
Rida Iftikhar ◽  
Harrison M. Penrose ◽  
Angelle N. King ◽  
Joshua S. Samudre ◽  
Morgan E. Collins ◽  
...  
Keyword(s):  
Stem Cells ◽  
Colon Cancer ◽  
Cancer Stem Cells ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Increased Risk

AbstractObesity is a worldwide epidemic associated with increased risk and progression of colon cancer. Here, we aimed to determine the role of adipose triglyceride lipase (ATGL), responsible for intracellular lipid droplet (LD) utilization, in obesity-driven colonic tumorigenesis. In local colon cancer patients, significantly increased ATGL levels in tumor tissue, compared to controls, were augmented in obese individuals. Elevated ATGL levels in human colon cancer cells (CCC) relative to non-transformed were augmented by an obesity mediator, oleic acid (OA). In CCC and colonospheres, enriched in colon cancer stem cells (CCSC), inhibition of ATGL prevented LDs utilization and inhibited OA-stimulated growth through retinoblastoma-mediated cell cycle arrest. Further, transcriptomic analysis of CCC, with inhibited ATGL, revealed targeted pathways driving tumorigenesis, and high-fat-diet obesity facilitated tumorigenic pathways. Inhibition of ATGL in colonospheres revealed targeted pathways in human colonic tumor crypt base cells (enriched in CCSC) derived from colon cancer patients. In CCC and colonospheres, we validated selected transcripts targeted by ATGL inhibition, some with emerging roles in colonic tumorigeneses (ATG2B, PCK2, PGAM1, SPTLC2, IGFBP1, and ABCC3) and others with established roles (MYC and MUC2). These findings demonstrate obesity-promoted, ATGL-mediated colonic tumorigenesis and establish the therapeutic significance of ATGL in obesity-reinforced colon cancer progression.

scholarly journals GDF15 Repression Contributes to 5-Fluorouracil Resistance in Human Colon Cancer by Regulating Epithelial-Mesenchymal Transition and Apoptosis

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Bin Wang ◽  
Nina Ma ◽  
Xixi Zheng ◽  
Xiao Li ◽  
Xiao Ma ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Growth Inhibition Assay ◽  
Colon Cells ◽  
Mesenchymal Transition

Chemotherapy based on 5-fluorouracil (5-FU) is the standard approach for colon cancer treatment, and resistance to 5-FU is a significant obstacle in the clinical treatment of colon cancer. However, the mechanisms underlying 5-FU resistance in colon cancer cells remain largely unknown. This study aimed at determining whether 5-FU-resistant colon cancer cells undergo epithelial-mesenchymal transition (EMT) and apoptosis and the role of GDF15—a member of the transforming growth factor β/bone morphogenetic protein super family and a protein known to be involved in cancer progression—in the regulation of EMT and apoptosis of these cells, along with the underlying mechanisms. In vitro apoptosis detection assay, growth inhibition assay, transwell, and wound healing experiments revealed that 5-FU-resistant colon cancer cells possessed enhanced EMT and antiapoptotic ability. These cells also showed a stronger tendency to proliferate and metastasize in vivo. Quantitative reverse transcription-PCR and western blotting revealed that 5-FU-resistant colon cancer cells expressed lower levels of growth differentiation factor 15 (GDF15) than did 5-FU-sensitive colon cancer cells. Moreover, the transient GDF15 overexpression resensitized 5-FU-resistant colon cells to 5-FU. Collectively, these findings indicate the mechanism underlying the 5-FU resistance of colon cancer cells and provide new therapeutic targets for improving the prognosis of colon cancer patients.

Role of SPARC in the epithelial mesenchymal transition induced by PTHrP in human colon cancer cells

2021 ◽  
pp. 111253
Author(s):  
Pedro Carriere ◽  
Natalia Calvo ◽  
María Belén Novoa ◽  
Fernanda Lopez-Moncada ◽  
Alexander Riquelme ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
Mesenchymal Transition ◽  
Human Colon Cancer Cells

scholarly journals Prevention of High Glucose-Mediated EMT by Inhibition of Hsp70 Chaperone

2021 ◽  
Vol 22 (13) ◽  
pp. 6902
Author(s):  
Alina D. Nikotina ◽  
Snezhana A. Vladimirova ◽  
Elena Y. Komarova ◽  
Dmitry Alexeev ◽  
Sergey Efremov ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Transcription Factors ◽  
Cell Motility ◽  
Cancer Cells ◽  
High Glucose ◽  
Binding Capacity ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
Hsp70 Chaperone ◽  
Migration Capacity

Hyperglycemia may contribute to the progression of carcinomas by triggering epithelial-to-mesenchymal transition (EMT). Some proteostasis systems are involved in metastasis; in this paper, we sought to explore the mechanism of Hsp70 chaperone in EMT. We showed that knockdown of Hsp70 reduced cell migration capacity concomitantly with levels of mRNA of the Slug, Snail, and Twist markers of EMT, in colon cancer cells incubated in high glucose medium. Conversely, treatment of cells with Hsp70 inducer U-133 were found to elevate cell motility, along with the other EMT markers. To prove that inhibiting Hsp70 may reduce EMT efficiency, we treated cells with a CL-43 inhibitor of the HSF1 transcription factor, which lowered Hsp70 and HSF1 content in the control and induced EMT in carcinoma cells. Importantly, CL-43 reduced migration capacity, EMT-linked transcription factors, and increased content of epithelial marker E-cadherin in colon cancer cells of three lines, including one derived from a clinical sample. To prove that Hsp70 chaperone should be targeted when inhibiting the EMT pathway, we treated cancer cells with 2-phenylethynesulfonamide (PES) and demonstrated that the compound inhibited substrate-binding capacity of Hsp70. Furthermore, PES suppressed EMT features, cell motility, and expression of specific transcription factors. In conclusion, the Hsp70 chaperone machine efficiently protects mechanisms of the EMT, and the safe inhibitors of the chaperone are needed to hamper metastasis at its initial stage.

Exosome-mediated delivery of functionally active miRNA-375-3p mimic regulate epithelial mesenchymal transition (EMT) of colon cancer cells

Life Sciences ◽  
2021 ◽  
Vol 269 ◽  
pp. 119035
Author(s):  
Ramazan Rezaei ◽  
Kaveh Baghaei ◽  
Davar Amani ◽  
Andrea Piccin ◽  
Seyed Mahmoud Hashemi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition

scholarly journals Invasive Colon Cancer Cells Induce Transdifferentiation of Endothelium to Cancer-Associated Fibroblasts through Microtubules Enriched in Tubulin-β3

2018 ◽  
Vol 20 (1) ◽  
pp. 53 ◽  
Author(s):  
Marta Wawro ◽  
Katarzyna Chojnacka ◽  
Katarzyna Wieczorek-Szukała ◽  
Katarzyna Sobierajska ◽  
Jolanta Niewiarowska
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Associated Fibroblasts ◽  
Colon Cancer Cells ◽  
Migration Ability ◽  
Mesenchymal Transition ◽  
Cytoskeleton Reorganization ◽  
Advanced Stages ◽  
Endothelial To Mesenchymal Transition ◽  
And Migration

Colon cancer, the second leading cause of cancer-related deaths in the world, is usually diagnosed in invasive stages. The interactions between cancer cells and cells located in their niche remain the crucial mechanism inducing tumor metastasis. The most important among those cells are cancer-associated fibroblasts (CAFs), the heterogeneous group of myofibroblasts transdifferentiated from numerous cells of different origin, including endothelium. The endothelial-to-mesenchymal transition (EndMT) is associated with modulation of cellular morphology, polarization and migration ability as a result of microtubule cytoskeleton reorganization. Here we reveal, for the first time, that invasive colon cancer cells regulate EndMT of endothelium via tubulin-β3 upregulation and its phosphorylation. Thus, we concluded that therapies based on inhibition of tubulin-β3 expression or phosphorylation, or blocking tubulin-β3’s recruitment to the microtubules, together with anti-inflammatory chemotherapeutics, are promising means to treat advanced stages of colon cancer.

scholarly journals Anti-ROR1 functionalised PLGA nanoparticles modulate metastatic and EMT biomarkers via cellular uptake of curcumin and ICA in colon cancer cells SW480

2020 ◽  
Author(s):  
Shamim Sufi ◽  
Muddasarul Hoda ◽  
Sankar Pajaniradje ◽  
Victor Mukherjee ◽  
Sultana Parveen ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cellular Uptake ◽  
Isothermal Calorimetry ◽  
Cell Surface Receptor ◽  
In Vivo Studies ◽  
Active Targeting ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
Surface Functionalisation

The challenge of next-generation nanoparticles (NPs) includes limited cellular uptake and loss by phagocytosis. General surface modification of NPs potentially enhances evasion from phagocytosis. However, active targeting and enhanced cellular uptake of nanoparticles are possible by surface functionalisation with molecules that have selective affinity for cancer cells. ROR1 is a cell surface receptor that is over-expressed in cancer cells. Hence, its conjugate antibody could be a potential surface functionalisation molecule. In the current study, anti-ROR1 antibody has been covalently attached to nanoparticles’ surface, thereby imparting its active targeting potential. Physicochemical and in vitro characterisations of the antibody-conjugated nanoparticles were performed. Surface functionalisation of nanoparticles was confirmed by scanning electron microscopy, isothermal calorimetry, and elemental analysis. Additionally, biomarkers of metastasis and epithelial-mesenchymal transition (EMT) were studied. Anti-ROR1 mAb tagged nanoparticles further confirmed therapeutic efficacy against colon cancer cells, SW480, thus, opening scope for further in vivo studies.

Sign in / Sign up

Export Citation Format

Share Document