Escherichia coli foster bladder cancer cell line progression via epithelial mesenchymal transition, stemness and metabolic reprogramming

Abd-El-Raouf, Romaila; Ouf, Salama A.; Gabr, Mahmoud M.; Zakaria, Mahmoud M.; El-Yasergy, Khaled F.; Ali‐El‐Dein, Bedeir

doi:10.1038/s41598-020-74390-5

Cited by 24 publications

(22 citation statements)

References 37 publications

(64 reference statements)

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“…Upon correlating the OXPHOS signature with the Hallmark EMT scores, we found that although there were significant correlations both in the positive and negative directions, there were many more datasets correlated negatively (56 vs. 24) with Hallmark EMT than were correlated positively (Fig 2A). This overall observation is in accordance with many experimental studies that point towards a negative association between oxidative phosphorylation and EMT [36][37][38][39]. However, this relationship is not exclusive, i.e.…”

Section: Oxphos Is More Likely To Be Negatively Correlated With a Mesenchymal Program And Positively With An Epithelial Onesupporting

confidence: 92%

Quantifying the patterns of metabolic plasticity and heterogeneity along the epithelial-hybrid-mesenchymal spectrum in cancer

Muralidharan

Sahoo

Saha

et al. 2021

Preprint

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Cancer metastasis is the leading cause of cancer-related mortality and the process of Epithelial to Mesenchymal Transition (EMT) is crucial for cancer metastasis. Either a partial or complete EMT have been reported to influence the metabolic plasticity of cancer cells in terms of switching among oxidative phosphorylation, fatty acid oxidation and glycolysis pathways. However, a comprehensive analysis of these major metabolic pathways their associations with EMT across different cancers is lacking. Here, we analyse more than 180 cancer cell datasets and show diverse associations of these metabolic pathways with the EMT status of cancer cells. Our bulk data analysis shows that EMT generally positively correlates with glycolysis but negatively with oxidative phosphorylation and fatty acid metabolism. These correlations are also consistent at the level of their molecular master regulators, namely AMPK and HIF1α. Yet, these associations are shown to not be universal. Analysis of single-cell data of EMT induction shows dynamic changes along the different axes of metabolic pathways, consistent with general trends seen in bulk samples. Together, our results reveal underlying patterns of metabolic plasticity and heterogeneity as cancer cells traverse through the epithelial-hybrid-mesenchymal spectrum of states.

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Section: Oxphos Is More Likely To Be Negatively Correlated With a Mesenchymal Program And Positively With An Epithelial Onesupporting

confidence: 92%

Quantifying the patterns of metabolic plasticity and heterogeneity along the epithelial-hybrid-mesenchymal spectrum in cancer

Muralidharan

Sahoo

Saha

et al. 2021

Preprint

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“…Hyaluronic acid (HA) is the main ligand for CD44, which is a constituent of the extracellular matrix (ECM) and it is expressed by stromal and cancer cells. It illustrated that CD44 may serve as microorganisms binding site, so that E. coli could bind to HA adherent to CD44 on urothelial cells, which facilitates E. coli migration through epithelial cells [31]. Interestingly, when a biofilm is detected on a tumor, its flanking normal tissue is mostly also covered by biofilm, suggesting that it expands over long distances in the tumor environment.…”

Section: Resultsmentioning

confidence: 99%

BIOFILM AND TUMOR: INTERPRETATION OF INTERACTION AND TREATMENT STRATEGIES. Review

Ivanenko

2021

Med. Sci. of Ukr.

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Relevance. Treatment of solid tumors and biofilm-derived infections face a common problem: drugs often fail to reach and kill cancer cells and microbial pathogens because of local microenvironment heterogeneities. There are remarkable challenges for current and prospective anticancer and antibiofilm agents to target and maintain activity in the microenvironments where cancer cells and microbial pathogens survive and cause the onset of disease. Bacterial infections in cancer formation will increase in the coming years. Collection of approaches such as ROS modulation in cells, the tumor is promoted by microbe’s inflammation can be a strategy to target cancer and bacteria. Besides that, bacteria may take the advantage of oxygen tension and permissive carbon sources, therefore the tumor microenvironment (TM) becomes a potential refuge for bacteria. It is noteworthy that the relationship between cancer and bacteria is intertwined. Objective: To analyze similarities between biofilm and tumor milieu that is produced against stress conditions and heterogeneous microenvironment for a combination of approaches the bacteriotherapy with chemotherapy which can help in defeating the tumor heterogeneity accompanied with malignancy, drug-resistance, and metastasis. Method: An analytical review of the literature on keywords from the scientometric databases PubMed, Wiley. Results: Bacteria evade antimicrobial treatment is mainly due to persistence that has become dormant during the stationary phase and tolerance. Drug-tolerant persisters and cellular dormancy are crucial in the development of cancer, especially in understanding the development of metastases as a late relapse. Bioﬁlms are formed by groups of cells in diﬀerent states, growing or non-growing and metabolically active or inactive in variable fractions, depending on maturity and on chemical gradients (O2 and nutrients) of the bioﬁlms producing physiological heterogeneity. Heterogeneity in the microenvironment of cancer can be described as a non-cell autonomous driver of cancer cell diversity; in a highly diverse microenvironment, different cellular phenotypes may be selected for or against in different regions of the tumor. Hypoxia, oxidative stress, and inflammation have been identified as positive regulators of metastatic potential, drug resistance, and tumorigenic properties in cancer. It is proven that, Escherichia coli (E. coli) and life-threatening infectious pathogens such as Staphylococcus aureus (SA) and Mycobacterium tuberculosis (Mtb) are noticeably sensitive to alterations in the intracellular oxidative environment. An alternative emerging paradigm is that many cancers may be promoted by commensal microbiota, either by translocation and adherence of microbes to cancer cells or by the distant release of inflammation-activating microbial metabolites. Microbial factors such as F. nucleatum, B. fragilis, and Enterobacteriaceae members may contribute to disease onset in patients with a hereditary form of colorectal cancer (CRC); familial adenomatous polyposis (FAP). These findings are linked with the creation of new biomarkers and therapy for identifying and treating biofilm-associated cancers. Currently, about 20% of neoplasms globally can be caused by infections, with approximately 1.2 million cases annually. Several antineoplastic drugs that exhibited activity against S. mutans, including tamoxifen, doxorubicin, and ponatinib, also possessed activity against other Gram-positive bacteria. Drug repurposing, also known as repositioning, has gained momentum, mostly due to its advantages over de novo drug discovery, including reduced risk to patients due to previously documented clinical trials, lower drug development costs, and faster benchtop-to-clinic transition. Although many bacteria are carcinogens and tumor promoters, some have shown great potential towards cancer therapy. Several species of bacteria have shown an impressive power to penetrate and colonize solid tumors, which has mainly led to neoplasm slower growth and tumor clearance. Different strains of Clostridia, Lactococcus, Bifidobacteria, Shigella, Vibrio, Listeria, Escherichia, and Salmonella have been evaluated against cancer in animal models. Conclusion. Cancer is a multifactorial disease and the use of bacteria for cancer therapy as an immunostimulatory agent or as a vector for carrying the therapeutic cargo is a promising treatment method. Therefore, the world has turned to an alternative solution, which is the use of genetically engineered microorganisms; thus, the use of living bacteria targeting cancerous cells is the unique option to overcome these challenges. Bacterial therapies, whether used alone or combination with chemotherapy, give a positive effect to treat multiple conditions of cancer.

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“…While previous research has examined the relationship between intra-tumoral microbes and EMT, almost no study examined such a relationship in MIBC or other forms of bladder cancers. The sole study that has explored this topic, to the best of our knowledge, found that urinary E. coli isolated from a bladder cancer patient was able to promote EMT in bladder cancer cell lines [20]. However, this study only profiled one bacterial species derived from a single patient.…”

Section: Discussionmentioning

confidence: 98%

The Bladder Microbiome Is Associated with Epithelial–Mesenchymal Transition in Muscle Invasive Urothelial Bladder Carcinoma

Iyangar

Reddy

et al. 2021

Cancers

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The intra-tumor microbiome has recently been linked to epithelial–mesenchymal transition (EMT) in a number of cancers. However, the relationship between EMT and microbes in bladder cancer has not been explored. In this study, we profiled the abundance of individual microbe species in the tumor samples of over 400 muscle invasive bladder carcinoma (MIBC) patients. We then correlated microbe abundance to the expression of EMT-associated genes and genes in the extracellular matrix (ECM), which are key players in EMT. We discovered that a variety of microbes, including E. coli, butyrate-producing bacterium SM4/1, and a species of Oscillatoria, were associated with expression of classical EMT-associated genes, including E-cadherin, vimentin, SNAI2, SNAI3, and TWIST1. We also found significant correlations between microbial abundance and the expression of genes in the ECM, specifically collagens and elastin. Lastly, we found that a large number of microbes exhibiting significant correlations to EMT are also associated with clinical prognosis and outcomes. We further determined that the microbes we profiled were likely not environmental contaminants. In conclusion, we discovered that the intra-tumoral microbiome could potentially play a significant role in the regulation of EMT in MIBC.

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Escherichia coli foster bladder cancer cell line progression via epithelial mesenchymal transition, stemness and metabolic reprogramming

Cited by 24 publications

References 37 publications

Quantifying the patterns of metabolic plasticity and heterogeneity along the epithelial-hybrid-mesenchymal spectrum in cancer

Quantifying the patterns of metabolic plasticity and heterogeneity along the epithelial-hybrid-mesenchymal spectrum in cancer

BIOFILM AND TUMOR: INTERPRETATION OF INTERACTION AND TREATMENT STRATEGIES. Review

The Bladder Microbiome Is Associated with Epithelial–Mesenchymal Transition in Muscle Invasive Urothelial Bladder Carcinoma

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