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- Denisenko, TV, et al.
(författare)
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Mitophagy in carcinogenesis and cancer treatment
- 2021
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Ingår i: Discover. Oncology. - : Springer Science and Business Media LLC. - 2730-6011. ; 12:1, s. 58-
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Tidskriftsartikel (refereegranskat)abstract
- In order to maintain a functional mitochondrial network, cells have developed a quality control mechanism, namely mitophagy. This process can be induced through different pathways. The most studied is the so-called PINK1/Parkin pathway, which is associated with ubiquitylation of several mitochondrial proteins that were initially found to be related to Parkinson’s disease. Another type of mitophagy is known as receptor-mediated mitophagy, which includes proteins, such as BNIP3 and BNIP3L, also known as Nix. Through these two mechanisms, mitophagy fulfills its functions and maintains cellular homeostasis. Here, we summarize the current knowledge about the mechanisms of mitophagy regulation and their interplay with cancer progression as well as anticancer treatment.
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- Nordström, Anders
(författare)
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Combining metabolic phenotype determination with metabolomics and transcriptional analyses to reveal pathways regulated by hydroxycarboxylic acid receptor 2
- 2022
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Ingår i: Discover Oncology. - : Springer Science and Business Media LLC. - 1868-8497 .- 2730-6011. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background The adaptation of cellular metabolism is considered a hallmark of cancer. Oncogenic signaling pathways support tumorigenesis and cancer progression through the induction of certain metabolic phenotypes associated with altered regulation of key metabolic enzymes. Hydroxycarboxylic acid receptor 2 (HCA(2)) is a G protein-coupled receptor previously shown to act as a tumor suppressor. Here, we aimed to unveil the connection between cellular metabolism and HCA(2) in BT-474 cells. Moreover, we intend to clarify how well this metabolic phenotype is reflected in transcriptional changes and metabolite levels as determined by global metabolomics analyses. Methods We performed both, siRNA mediated knockdown of HCA(2) and stimulation with the HCA(2)-specific agonist monomethyl fumarate. Seahorse technology was used to determine the role of HCA(2) in BT-474 breast cancer cell metabolism and its potential to induce a switch in the metabolic phenotype in the presence of different energy substrates. Changes in the mRNA expression of metabolic enzymes were detected with real-time quantitative PCR (RT-qPCR). Untargeted liquid chromatography-mass spectrometry (LC-MS) metabolic profiling was used to determine changes in metabolite levels. Results Knockdown or stimulation of HCA(2) induced changes in the metabolic phenotype of BT474 cells dependent on the availability of energy substrates. The presence of HCA(2) was associated with increased glycolytic flux with no fatty acids available. This was reflected in the increased mRNA expression of the glycolytic enzymes PFKFB4 and PKM2, which are known to promote the Warburg effect and have been described as prognostic markers in different types of cancer. With exogenous palmitate present, HCA(2) caused elevated fatty acid oxidation and likely lipolysis. The increase in lipolysis was also detectable at the transcriptional level of ATGL and the metabolite levels of palmitic and stearic acid. Conclusions We combined metabolic phenotype determination with metabolomics and transcriptional analyses and identified HCA(2) as a regulator of glycolytic flux and fatty acid metabolism in BT-474 breast cancer cells. Thus, HCA(2), for which agonists are already widely used to treat diseases such as psoriasis or hyperlipidemia, may prove useful as a target in combination cancer therapy.
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- Schindele, Alexandra, et al.
(författare)
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Mapping human papillomavirus, Epstein–Barr virus, cytomegalovirus, adenovirus, and p16 in laryngeal cancer
- 2022
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Ingår i: Discover Oncology. - : Springer. - 2730-6011. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Apart from tobacco and alcohol, viral infections are proposed as risk factors for laryngeal cancer. The occurrence of oncogenic viruses including human papilloma virus (HPV) and Epstein–Barr virus (EBV), in laryngeal squamous cell carcinoma (LSCC) varies in the world. Carcinogenesis is a multi-step process, and the role of viruses in LSCC progression has not been clarified. We aimed to analyze the presence and co-expression of HPV, EBV, human cytomegalovirus (HCMV) and human adenovirus (HAdV) in LSCC. We also investigated if p16 can act as surrogate marker for HPV in LSCC.Methods: Combined PCR/microarrays (PapilloCheck®) were used for detection and genotyping of HPV DNA, real-time PCR for EBV, HCMV and HAdV DNA detection, and EBER in situ hybridization (EBER-ISH) for EBV detection in tissue from 78 LSCC patients. Additionally, we analyzed p16 expression with immunohistochemistry.Results: Thirty-three percent (26/78) of LSCC tumor samples were EBV positive, 9% (7/78) HCMV positive and 4% (3/78) HAdV positive. Due to DNA fragmentation, 45 samples could not be analyzed with PapilloCheck®; 9% of the remaining (3/33) were high-risk HPV16 positive and also over-expressed p16. A total of 14% (11/78) of the samples over-expressed p16.Conclusion: These findings present a mapping of HPV, EBV, HCMV and HAdV, including the HPV surrogate marker p16, in LSCC in this cohort. Except for EBV, which was detected in a third of the samples, data show viral infection to be uncommon, and that p16 does not appear to be a specific surrogate marker for high-risk HPV infection in LSCC.
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