FATP2 regulates non-small cell lung cancer by mediating lipid metabolism through ACSL1

Chen, Yinghua; Zhao, Yu; Deng, Yuan; Yang, Yan; Xu, Lijun; Fu, Jianwei

doi:10.1016/j.tice.2023.102105

Cited by 4 publications

(3 citation statements)

References 42 publications

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“…ACSL3 is an unfavorable prognostic marker in liver cancer and lung cancer. ACSL6 is a favorable prognostic marker in leukemia [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, each ACSL family member has different effects on lung cancer. According to the results from the Oncomine and PrognoScan databases, ACSL1 is modestly expressed in lung carcinoma, negatively correlated with fatty acid transport protein 2 (FATP2), and the interaction between ACSL1 and FATP2 promotes non-small-cell lung cancer (NSCLC) cell progression [ 13 ]. ACSL3-mediated fatty acid oxidation is required for mutant KRAS lung tumorigenesis [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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The Diagnostic Value of ACSL1, ACSL4, and ACSL5 and the Clinical Potential of an ACSL Inhibitor in Non-Small-Cell Lung Cancer

Ma,

Nenkov,

Berndt

et al. 2024

Cancers

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Abnormal expression of ACSL members 1, 3, 4, 5, and 6 is frequently seen in human cancer; however, their clinical relevance is unclear. In this study, we analyzed the expression of ACSLs and investigated the effects of the ACSL inhibitor Triacsin C (TC) in lung cancer. We found that, compared to normal human bronchial epithelial (NHBE) cells, ACSL1, ACSL4, and ACSL6 were highly expressed, while ACSL3 and ACSL5 were lost in the majority of lung cancer cell lines. ACSL activity was associated with the expression levels of the ACSLs. In primary lung tumors, a higher expression of ACSL1, ACSL4, and ACSL5 was significantly correlated with adenocarcinoma (ADC). Moreover, ACSL5 was significantly reversely related to the proliferation marker Ki67 in low-grade tumors, while ACSL3 was positively associated with Ki67 in high-grade tumors. Combination therapy with TC and Gemcitabine enhanced the growth-inhibitory effect in EGFR wild-type cells, while TC combined with EGFR-TKIs sensitized the EGFR-mutant cells to EGFR-TKI treatment. Taken together, the data suggest that ACSL1 may be a biomarker for lung ADC, and ACSL1, ACSL4, and ACSL5 may be involved in lung cancer differentiation, and TC, in combination with chemotherapy or EGFR-TKIs, may help patients overcome drug resistance.

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“…ACSL3 is an unfavorable prognostic marker in liver cancer and lung cancer. ACSL6 is a favorable prognostic marker in leukemia [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Diagnostic Value of ACSL1, ACSL4, and ACSL5 and the Clinical Potential of an ACSL Inhibitor in Non-Small-Cell Lung Cancer

Ma,

Nenkov,

Berndt

et al. 2024

Cancers

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“…SLC27A2 (aka FATP2, VLCAS) mediates the import of long-chain fatty acids into the cell and is a peroxisomal very long-chain acyl-CoA synthetase (Hirsch et al, 1998;Uchiyama et al, 1996). SLC27A2 regulates non-small-cell lung cancer (Chen et al, 2023) and kidney fibrosis (Chen et al, 2020) through its effect on lipid metabolism. A high level of NHLRC2 has been associated with shortened survival in lung adenocarcinoma, a type of non-small-cell lung cancer (Kreus et al, 2023).…”

Section: Discussionmentioning

confidence: 99%

FINCA disease mouse model exhibits altered behaviour and immune response

Hiltunen,

Kangas,

Gondane

et al. 2024

Preprint

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Fibrosis, neurodegeneration and cerebral angiomatosis (FINCA) is a childhood-onset multi-organ neurodevelopmental disorder associated with multi-organ manifestations and recurrent infections. The disease is caused by variants inNHLRC2initiating a cascade of unknown pathological events. Previously, we have demonstrated that despite the significant decrease at the molecular level, the compound heterozygosity of knock out and p.Asp148Tyr alleles in NHLRC2 does not lead to a severe phenotype in mice. Here, we analysed the behavioural and immunological phenotype of the FINCA mice and studied the molecular pathways affected by p.Asp148Tyr in NHLRC2 using mouse and human-derived cell culture models. The FINCA mice displayed a mild hyperactivity and deficient early immune response when challenged with LPS leading to altered cytokine responses, including IFNγ, IL-12, and TNFα. By comparing gene expression and putative interaction partners affected by p.Asp148Tyr, we identified Rho GTPase signalling as the common pathway. Altogether, these results establish a multi-dimensional impact of the p.Asp148Tyr variant in NHLRC2. Knowledge of the molecular pathways affected by NHLRC2 and the natural course of FINCA disease progression are instrumental for the development of effective therapeutics.Summary statementFINCA is a paediatric neurodevelopmental and multi-organ disorder caused by variants inNHLRC2. Here, mild hyperactivity in connection with altered early immune response is described in the FINCA mouse model.

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Regulation of cancer cell lipid metabolism and oxidative phosphorylation by microenvironmental acidosis

Rolver,

Severin,

Pedersen

2024

American Journal of Physiology-Cell Physiology

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The expansion of cancer cell mass in solid tumors generates a harsh environment characterized by dynamically varying levels of acidosis, hypoxia and nutrient deprivation. Because acidosis inhibits glycolytic metabolism and hypoxia inhibits oxidative phosphorylation, cancer cells that survive and grow in these environments must rewire their metabolism and develop a high degree of metabolic plasticity to meet their energetic and biosynthetic demands. Cancer cells frequently upregulate pathways enabling the uptake and utilization of lipids and other nutrients derived from dead or recruited stromal cells, and in particular lipid uptake is strongly enhanced in acidic microenvironments. The resulting lipid accumulation and increased reliance on β-oxidation and mitochondrial metabolism increases susceptibility to oxidative stress, lipotoxicity and ferroptosis, in turn driving changes that may mitigate such risks. The spatially and temporally heterogeneous tumor microenvironment thus selects for invasive, metabolically flexible, and resilient cancer cells capable of exploiting their local conditions as well as of seeking out more favorable surroundings. This phenotype relies on the interplay between metabolism, acidosis and oncogenic mutations, driving metabolic signaling pathways such as peroxisome proliferator-activated receptors (PPARs). Understanding the particular vulnerabilities of such cells may uncover novel therapeutic liabilities of the most aggressive cancer cells.

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FATP2 regulates non-small cell lung cancer by mediating lipid metabolism through ACSL1

Cited by 4 publications

References 42 publications

The Diagnostic Value of ACSL1, ACSL4, and ACSL5 and the Clinical Potential of an ACSL Inhibitor in Non-Small-Cell Lung Cancer

The Diagnostic Value of ACSL1, ACSL4, and ACSL5 and the Clinical Potential of an ACSL Inhibitor in Non-Small-Cell Lung Cancer

FINCA disease mouse model exhibits altered behaviour and immune response

Regulation of cancer cell lipid metabolism and oxidative phosphorylation by microenvironmental acidosis

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