ANKRD22, a novel tumor microenvironment-induced mitochondrial protein promotes metabolic reprogramming of colorectal cancer cells

Objective: The tumor microenvironment has a crucial role in organizing cancer malignancy, progression, drug resistance and survival. It consists of cellular and non-cellular components. These non-cellular components such as cytokines, extracellular matrix, growth factors and metabolites are responsible for shifting the action from pro-cancer to anti-cancer effects. Twenty percent of all cancers occur in association with chronic inflammation via cytokines. Even cancers that are not caused by chronic inflammation, present high levels of cytokine expression pattern in their tumor microenvironment. Tumor necrosis factor-alpha (TNF-α) and some interleukins are characterized as pro-tumorigenic cytokines and they were involved in cancer by presenting their ability to activate the oncogenic transcription factors. The aim of this study is to evaluate the remodeling of colorectal cancer tumor microenvironment by TNF-α. Material and Methods: TNF-α (5ng/ml) was applied to HT-29 colorectal cancer cells, then human soluble factors were determined by using Human Cytokine Group 1, 8 plex Panel (Bio-Rad Laboratories Inc. USA) and Magpix Luminex instrument and xPONENT software (version 4.2, Luminex Corp, Austin, Texas, US). The results were normalized to total protein concentration estimated via Bradford assay. Results: Current research highlights the effect of TNF-α on the tumor microenvironment. Interleukin-6 and interleukin -8 soluble factors were higher in TNF-α treated colorectal cancer cells when compared with untreated control group. Conclusion: The results of the study show that TNF-α is responsible for elevating the levels of interleukin-6 and interleukin-8, which are associated with inflammation in the tumor microenvironment. Key words: Colorectal Cancer, Tumor Microenvironment, Cytokines, TNF-α, Interleukin-6, interleukin -8

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Resveratrol Suppresses Cross-Talk between Colorectal Cancer Cells and Stromal Cells in Multicellular Tumor Microenvironment: A Bridge between In Vitro and In Vivo Tumor Microenvironment Study

Molecules ◽

10.3390/molecules25184292 ◽

2020 ◽

Vol 25 (18) ◽

pp. 4292

Author(s):

Constanze Buhrmann ◽

Parviz Shayan ◽

Aranka Brockmueller ◽

Mehdi Shakibaei

Keyword(s):

Colorectal Cancer ◽

Tumor Microenvironment ◽

T Lymphocytes ◽

Cancer Cells ◽

T Lymphocyte ◽

Stromal Cells ◽

Colorectal Cancer Cells ◽

Hct116 Cells

The interaction between tumor cells and the tumor microenvironment (TME) is an important process for the development of tumor malignancy. Modulation of paracrine cross-talk could be a promising strategy for tumor control within the TME. The exact mechanisms of multi-targeted compound resveratrol are not yet fully understood. Whether resveratrol can modulate paracrine signal transduction-induced malignancy in the multicellular-TME of colorectal cancer cells (CRC) was investigated. An in vitro model with 3D-alginate HCT116 cells in multicellular-TME cultures (fibroblast cells, T-lymphocytes) was used to elucidate the role of TNF-β, Sirt1-ASO and/or resveratrol in the proliferation, invasion and cancer stem cells (CSC) of CRC cells. We found that multicellular-TME, similar to TNF-β-TME, promoted proliferation, colony formation, invasion of CRC cells and enabled activation of CSCs. However, after co-treatment with resveratrol, the malignancy of multicellular-TME reversed to HCT116. In addition, resveratrol reduced the secretion of T-lymphocyte/fibroblast (TNF-β, TGF-β3) proteins, antagonized the T-lymphocyte/fibroblast-promoting NF-κB activation, NF-κB nuclear translocation and thus the expression of NF-κB-promoting biomarkers, associated with proliferation, invasion and survival of CSCs in 3D-alginate cultures of HCT116 cells induced by TNF-β- or multicellular-TME, but not by Sirt1-ASO, indicating the central role of this enzyme in the anti-tumor function of resveratrol. Our results suggest that in vitro multicellular-TME promotes crosstalk between CRC and stromal cells to increase survival, migration of HCT116 and the resveratrol/Sirt1 axis suppresses this loop by modulating paracrine agent secretion and NF-κB signaling. Fibroblasts and T-lymphocytes are promising targets for resveratrol in the prevention of CRC metastasis.

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Hypoxic colorectal cancer-secreted exosomes deliver miR-210-3p to normoxic tumor cells to elicit a protumoral effect

Experimental Biology and Medicine ◽

10.1177/15353702211011576 ◽

2021 ◽

pp. 153537022110115

Author(s):

Liuqing Ge ◽

Feng Zhou ◽

Jiayan Nie ◽

Xiaobing Wang ◽

Qiu Zhao

Keyword(s):

Colorectal Cancer ◽

Tumor Microenvironment ◽

Cancer Cells ◽

Tumor Cells ◽

Cancer Progression ◽

Preclinical Study ◽

Mechanistic Investigation ◽

Colorectal Cancer Cells ◽

Colorectal Cancer Progression

Hypoxia, the most common feature in the tumor microenvironment, is closely related to tumor malignant progression and poor patient’s prognosis. Exosomes, initially recognized as cellular “garbage dumpsters”, are now known to be important mediums for mediating cellular communication in tumor microenvironment. However, the mechanisms of hypoxic tumor cell-derived exosomes facilitate colorectal cancer progression still need further exploration. In the present study, we found that exosomes from hypoxic colorectal cancer cells (H-Exos) promoted G1-S cycle transition and proliferation while preventing the apoptosis of colorectal cancer cells by transmitting miR-210-3p to normoxic tumor cells. Mechanistic investigation indicated that miR-210-3p from H-Exos elicited its protumoral effect via suppressing CELF2 expression. A preclinical study further confirmed that H-Exos could promote tumorigenesis in vivo. Clinically, the expression of miR-210-3p in circulating plasma exosomes was markedly upregulated in colorectal cancer patients, which were closely associated with multiple unfavorable clinicopathological features. Taken together, these results suggest that hypoxia may stimulate colorectal cancer cells to secrete miR-210-3p-enriched exosomes in tumor microenvironment, which elicit protumoral effects by inhibiting CELF2 expression. These findings provide new insights on the mechanism of colorectal cancer progression and potential therapeutic targets for colorectal cancer.

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Identification of biological processes and signaling pathways for the knockout of C14orf159 in colorectal cancer cells

10.31219/osf.io/chyku ◽

2021 ◽

Author(s):

Min Zhang ◽

Jing Wang ◽

Hanming Gu

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Signaling Pathways ◽

Lupus Erythematosus ◽

Homo Sapiens ◽

Mitochondrial Protein ◽

Biological Processes ◽

Illumina Hiseq ◽

Colorectal Cancer Cells ◽

Matrix Metallopeptidase

Functional mitochondria are crucial to the development and metastasis of cancer cells. C14orf159 is an important mitochondrial protein and is associated with the proliferation of cancer cells. In our study, we aim to identify essential signaling pathways and biological processes in the knockout of C14orf159 in colorectal cancer cells. The GSE167947 dataset was produced by using the Illumina HiSeq 2500 (Homo sapiens). The KEGG and GO analyses showed that biological processes “Staphylococcus aureus infection” and “Systemic lupus erythematosus” are the most important processes in the loss of C14orf159. Moreover, we identified a variety of genes by constructing the PPI network, which includes Albumin, Brain derived neurotrophic factor, and Matrix metallopeptidase 9. Therefore, our study provides insights into the treatment of colorectal cancer by targeting mitochondria.

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