Targeting the lipid metabolic axis ACSL/SCD in colorectal cancer progression by therapeutic miRNAs: miR-19b-1 role

Cruz-Gil, Silvia; Martínez, Rubén; Cedrón, Marta Gómez de; Martín‐Hernández, Roberto; Vargas, Teodoro; Molina, Susana; Herránz, Jesús; Dávalos, Alberto; Reglero, Guillermo; Molina, Ana Ramı́rez de

doi:10.1194/jlr.m076752

Cited by 55 publications

(41 citation statements)

References 39 publications

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“…This activation of fatty acids by ACSL is a necessary step for the synthesis of cellular lipids as well as the β-oxidation. In colon cancer cells increased expression of ACSL1 and ACSL4 is associated with EMT features of these cells (273). The mechanism is not clear but one report suggests that this offers a metabolic advantage in the cancer cells by making them more energy efficient and by increasing the expression of SNAIL2 and Ncadherin (274).…”

Section: Lipid Metabolismmentioning

confidence: 99%

EMT Factors and Metabolic Pathways in Cancer

Georgakopoulos-Soares

et al. 2020

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The epithelial-mesenchymal transition (EMT) represents a biological program during which epithelial cells lose their cell identity and acquire a mesenchymal phenotype. EMT is normally observed during organismal development, wound healing and tissue fibrosis. However, this process can be hijacked by cancer cells and is often associated with resistance to apoptosis, acquisition of tissue invasiveness, cancer stem cell characteristics, and cancer treatment resistance. It is becoming evident that EMT is a complex, multifactorial spectrum, often involving episodic, transient or partial events. Multiple factors have been causally implicated in EMT including transcription factors (e.g., SNAIL, TWIST, ZEB), epigenetic modifications, microRNAs (e.g., miR-200 family) and more recently, long non-coding RNAs. However, the relevance of metabolic pathways in EMT is only recently being recognized. Importantly, alterations in key metabolic pathways affect cancer development and progression. In this review, we report the roles of key EMT factors and describe their interactions and interconnectedness. We introduce metabolic pathways that are involved in EMT, including glycolysis, the TCA cycle, lipid and amino acid metabolism, and characterize the relationship between EMT factors and cancer metabolism. Finally, we present therapeutic opportunities involving EMT, with particular focus on cancer metabolic pathways.

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Section: Lipid Metabolismmentioning

confidence: 99%

EMT Factors and Metabolic Pathways in Cancer

Georgakopoulos-Soares

et al. 2020

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“…Low expression of ACSL5 serves as a prognostic factor for early recurrence of colorectal carcinoma (32). The ACSL1/ACSL4/SCD lipid network enhances migration and invasion capacity by inducing epithelial-mesenchymal transition in colorectal cancer, and microRNA-19b-1 is a key regulator in this oncogenic axis (33,34). Additionally, high expression of ACSL5 may be used as a biomarker for predicting relatively favorable clinical outcomes in patients with breast cancer (35).…”

Section: Discussionmentioning

confidence: 99%

Regulatory mechanism of fatty acid‑CoA metabolic enzymes under endoplasmic reticulum stress in lung cancer

Liu

Yeh

Chou³

et al. 2018

Oncol Rep

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The endoplasmic reticulum (ER) is an organelle involved in various physiological processes such as lipid metabolism, protein synthesis and folding, and cellular calcium storage. In a physiological tumor microenvironment, hypoxia, nutrient deprivation, and calcium dysregulation cause accumulation of unfolded and misfolded proteins. Such accumulation induces ER stress and unfolded protein responses (UPRs). Increased UPR signaling pathways are associated with multiple types of cancer. The influence of ER stress on acyl‑CoA metabolic enzymes is not well understood. Evaluation of PRECOG and Kaplan‑Meier plotter databases in the present study suggested that high expression of acyl‑CoA thioesterase (ACOT)7, ACOT11, ACOT13, soluble carrier family 27 member A4 (SLC27A4) and SLC27A5 was associated with poor clinical outcomes. In addition, expression levels of ACOT7, ACOT11, SLC27A4 and SLC27A5 were not altered after induction of ER stress. By contrast, expression of some enzymes was decreased, such as those of long‑chain acyl‑CoA synthetase (ACSL)3, ACSL4 and SLC27A2. Fatty acid uptake capacity was suppressed in lung cancer cell lines A549 and CL1‑0 after thapsigargin treatment but intracellular reactive oxygen species levels were not suppressed. Gene enrichment and regulatory element analysis were performed; the results provided potential targets for further investigation. On the whole, our findings demonstrate the potential regulatory mechanism of high‑expression of acyl‑CoA metabolic enzymes, the biological effects of decreased enzyme expression levels, possible regulatory elements, and the interaction network involved in responses to ER stress in lung cancer.

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“…Однако последние сообщения по этому поводу в Японии, американских и европейских странах противоречивы [10,[28][29][30]. В мембранах эритроцитов уровень С18:0 оказался выше у больных КРР, чем у пациентов без КРР [31], хотя данные авторов неоднозначны [32][33][34][35][36].…”

Section: экспериментальные статьиunclassified

Study of the Level of Fatty Acids in Erythrocyte Membranes and Serum of Patients With Colorectal Cancer in Novosibirsk

et al. 2018

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The objectiveis to measure the level of fatty acids in erythrocyte membranes and serum of patients with colorectal cancer.Materials and methods.The study group included 100 patients with diagnosed colorectal cancer (57 men and 43 women). The control group included 24 reasonably healthy people (14 men and 10 women) matched for age and sex, without malignant cancers or manifested pathology of the internal organs.Results.Decreased levels of saturated, monounsaturated fatty acids and increased levels of polyunsaturated fatty acids (PUFAs) in erythrocyte membranes and serum (p <0.0001–0.05) were observed. The levels of omega-3 PUFAs in colorectal cancer exceeded the levels in healthy individuals both in erythrocyte membranes and in serum; for omega-6 PUFAs only a trend was observed. At the same time, the ratio of omega-6/omega-3 PUFAs in colorectal cancer was lower than in control (p <0.0001–0.002). The state of erythrocyte membranes more significantly and for more parameters characterized differences between the groups than serum. The most discriminating parameters between patients with colorectal cancer and healthy individuals both in erythrocyte membranes and serum were the levels of C20:2;11,14 (eicosadienoic), C20:3;8,11,14 (dihomo-γ-linolenic), C20:4;5,8,11,14 (eicosatetraenoic, arachidonic), C22:5;7,10,13,16,19 (docosapentaenoic), and C22:6;4,7,10,13,16,19 (docosahexaenoic) PUFAs.

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Targeting the lipid metabolic axis ACSL/SCD in colorectal cancer progression by therapeutic miRNAs: miR-19b-1 role

Cited by 55 publications

References 39 publications

EMT Factors and Metabolic Pathways in Cancer

EMT Factors and Metabolic Pathways in Cancer

Regulatory mechanism of fatty acid‑CoA metabolic enzymes under endoplasmic reticulum stress in lung cancer

Study of the Level of Fatty Acids in Erythrocyte Membranes and Serum of Patients With Colorectal Cancer in Novosibirsk

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