New discoveries in the molecular landscape of bladder cancer

Kamat, Ashish M.; Li, Roger; Choi, Woonyoung; Ferguson, James E.; Metcalfe, Michael

doi:10.12688/f1000research.10031.1

Cited by 4 publications

(2 citation statements)

References 48 publications

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“…Several metabolic altered pathways are involved in bladder tumorigenesis 27 . With the advancement of multi-omics analysis, de novo identification of oncogenes have been carried out in various types of cancers, including BLCA 28 . A most recent multi-omics study has shown that fatty acid metabolism plays a central role in facilitating the progress of BLCA 29 .…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Acetyl-CoA synthetase 3 promotes bladder cancer cell growth under metabolic stress

et al. 2020

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Cancer cells adapt to nutrient-deprived tumor microenvironment during progression via regulating the level and function of metabolic enzymes. Acetyl-coenzyme A (AcCoA) is a key metabolic intermediate that is crucial for cancer cell metabolism, especially under metabolic stress. It is of special significance to decipher the role acetyl-CoA synthetase short chain family (ACSS) in cancer cells confronting metabolic stress. Here we analyzed the generation of lipogenic AcCoA in bladder cancer cells under metabolic stress and found that in bladder urothelial carcinoma (BLCA) cells, the proportion of lipogenic AcCoA generated from glucose were largely reduced under metabolic stress. Our results revealed that ACSS3 was responsible for lipogenic AcCoA synthesis in BLCA cells under metabolic stress. Interestingly, we found that ACSS3 was required for acetate utilization and histone acetylation. Moreover, our data illustrated that ACSS3 promoted BLCA cell growth. In addition, through analyzing clinical samples, we found that both mRNA and protein levels of ACSS3 were dramatically upregulated in BLCA samples in comparison with adjacent controls and BLCA patients with lower ACSS3 expression were entitled with longer overall survival. Our data revealed an oncogenic role of ACSS3 via regulating AcCoA generation in BLCA and provided a promising target in metabolic pathway for BLCA treatment.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Acetyl-CoA synthetase 3 promotes bladder cancer cell growth under metabolic stress

et al. 2020

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“…Omics studies have identified therapeutic targets and resulted in the successful development of new drugs to treat various solid tumors like breast cancer and lung cancer (4,5). For bladder cancer, prognostication and treatment still depend mainly on pathologic and clinical characteristics (6). Patients diagnosed with high-grade invasive disease are difficult to treat effectively and have a relatively low life expectancy despite available multimodal therapies.…”

Section: Introductionmentioning

confidence: 99%

Multi-omics Integration Analysis Robustly Predicts High-Grade Patient Survival and Identifies CPT1B Effect on Fatty Acid Metabolism in Bladder Cancer

Vantaku

Dong

Ambati

et al. 2019

Clinical Cancer Research

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Purpose: The perturbation of metabolic pathways in high-grade bladder cancer has not been investigated. We aimed to identify a metabolic signature in high-grade bladder cancer by integrating unbiased metabolomics, lipidomics, and transcriptomics to predict patient survival and to discover novel therapeutic targets. Experimental Design: We performed high-resolution liquid chromatography mass spectrometry (LC-MS) and bioinformatic analysis to determine the global metabolome and lipidome in high-grade bladder cancer. We further investigated the effects of impaired metabolic pathways using in vitro and in vivo models. Results: We identified 519 differential metabolites and 19 lipids that were differentially expressed between low-grade and high-grade bladder cancer using the NIST MS metabolomics compendium and lipidblast MS/MS libraries, respectively. Pathway analysis revealed a unique set of biochemical pathways that are highly deregulated in high-grade bladder cancer. Integromics analysis identified a molecular gene signature associated with poor patient survival in bladder cancer. Low expression of CPT1B in high-grade tumors was associated with low FAO and low acyl carnitine levels in high-grade bladder cancer, which were confirmed using tissue microarrays. Ectopic expression of the CPT1B in high-grade bladder cancer cells led to reduced EMT in in vitro, and reduced cell proliferation, EMT, and metastasis in vivo. Conclusions: Our study demonstrates a novel approach for the integration of metabolomics, lipidomics, and transcriptomics data, and identifies a common gene signature associated with poor survival in patients with bladder cancer. Our data also suggest that impairment of FAO due to downregulation of CPT1B plays an important role in the progression toward high-grade bladder cancer and provide potential targets for therapeutic intervention.

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Targeted Treatments for Common Solid Tumors

2018

A Beginner's Guide to Targeted Cancer Treatments

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New discoveries in the molecular landscape of bladder cancer

Cited by 4 publications

References 48 publications

RETRACTED ARTICLE: Acetyl-CoA synthetase 3 promotes bladder cancer cell growth under metabolic stress

RETRACTED ARTICLE: Acetyl-CoA synthetase 3 promotes bladder cancer cell growth under metabolic stress

Multi-omics Integration Analysis Robustly Predicts High-Grade Patient Survival and Identifies CPT1B Effect on Fatty Acid Metabolism in Bladder Cancer

Targeted Treatments for Common Solid Tumors

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