https://doi.org/10.4081/ejh.2023.3867

Regulatory roles of ACSL5 in the anti-tumor function of palmitic acid (C16:0) via the ERK signaling pathway

Vol. 67 No. 4 (2023)
Submitted: 9 September 2023
Accepted: 24 October 2023
Published: 8 November 2023
Non-small lung cancer, palmitic acid (C16:0), Acyl-CoA synthase long chain family member 5, ERK signal pathway
Abstract Views: 532
PDF: 322
HTML: 11
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Jiapei Lv
lvjiapei_123@163.com
The Affiliated People’s Hospital of Ningbo University, Ningbo, Zhejiang, China.
Wang Yanting
Ningbo Zhenhai People’s Hospital, Ningbo, Zhejiang, China.
Shan Wei
The Affiliated People’s Hospital of Ningbo University, Ningbo, Zhejiang, China.

Previous studies have highlighted the susceptibility of cancer to perturbations in lipid metabolism. In particular, C16:0 has emerged as a promising novel treatment for hepatocellular carcinoma. In our study, we investigated the levels of C16:0 in the serum of non-small lung cancer patients were significant downregulation compared to healthy individuals (n=10; p<0.05). Moreover, our in vitro experiments using A549 cells demonstrated that C16:0 effectively inhibited proliferation, apoptosis, migration, and invasion. Despite these promising results, its pathogenesis remains poorly understood. CCK-8 assay, annexin V-FITC/PI double staining assay, wound healing assay and transwell assay were performed to evaluate the effects of C16:0, on proliferation, apoptosis, migration and invasion of A549 cells. RNA sequencing was used to identify essential factors involved in C16:0-growth inhibition in lung cancer. Further, the expression levels of related gene and proteins were detected by quantitative RT-PCR and Western blotting. Mouse NSCLC subcutaneous xenograft tumor model was established, and gastric lavage was given with C16:0. Tumor volume assay and hematoxylin-eosin staining were used to detect tumor growth in vivo. Our analysis revealed a significant upregulation of ACSL5 and its associated proteins in C16:0-treated A549 cells compared to the control group both in vivo and in vitro. Moreover, the knockdown of ACSL5 reversed the anti-tumor effect, resulting in an increased rate of the malignant phenotype mentioned above. Additionally, the expression of phosphorylated ERK protein was significantly inhibited with increasing concentrations of C16:0 in A549 cells. These results reveal for the first time that C16:0, as a novel target, regulates ACLS5 through the ERK signaling pathway, to inhibit the proliferation and apoptosis and inhibits cell migration and invasion of NSCLC. These findings may lead to the development of a novel therapeutic approach for non-small lung cancer.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Crossref
Scopus
Google Scholar
Europe PMC
Lv J, Zhang F, Wang X. Clinical lipidomics: a new way to diagnose human diseases. Clin Transl Med 2018; 7: 12. DOI: https://doi.org/10.1186/s40169-018-0190-9
Snaebjornsson MT, Janaki-Raman S, Schulze A. Greasing the wheels of the cancer machine: the role of lipid metabolism in cancer. Cell Metab 2020;31:62-76. DOI: https://doi.org/10.1016/j.cmet.2019.11.010
Doria ML, Cotrim Z, Macedo B, Simoes C, Domingues P, Helguero L, et al. Lipidomic approach to identify patterns in phospholipid profiles and define class differences in mammary epithelial and breast cancer cells. Breast Cancer Res Tr 2012;133:635-48. DOI: https://doi.org/10.1007/s10549-011-1823-5
Bu SY, Mashek DG. Hepatic long-chain acyl-CoA synthetase 5 mediates fatty acid channeling between anabolic and catabolic pathways. J Lipid Res 2010;51:3270-80. DOI: https://doi.org/10.1194/jlr.M009407
Fhaner CJ, Liu S, Ji H, Simpson RJ, Reid GE. Comprehensive lipidome profiling of isogenic primary and metastatic colon adenocarcinoma cell lines. Anal Chem 2012;84:8917-26. DOI: https://doi.org/10.1021/ac302154g
Ren J, Zhang D, Liu Y, Zhang R, Fang H, Guo S, et al. Simultaneous quantification of serum nonesterified and esterified fatty acids as potential biomarkers to differentiate benign lung diseases from lung cancer. Sci Rep 2016;6:34201. DOI: https://doi.org/10.1038/srep34201
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin 2021;71:7-33. Erratum in: CA Cancer J Clin 2021;71:359. DOI: https://doi.org/10.3322/caac.21654
Lv J, Gao D, Zhang Y, Wu D, Shen L, Wang X. Heterogeneity of lipidomic profiles among lung cancer subtypes of patients. J Cell Mol Med 2018;22:5155-9. DOI: https://doi.org/10.1111/jcmm.13782
Zhang L, Lv J, Chen C, Wang X. Roles of acyl-CoA synthetase long-chain family member 5 and colony stimulating factor 2 in inhibition of palmitic or stearic acids in lung cancer cell proliferation and metabolism. Cell Biol Toxicol 2021;37:15-34. DOI: https://doi.org/10.1007/s10565-020-09520-w
Soupene E, Kuypers FA. Mammalian long-chain acyl-CoA synthetases. Exp Biol Med 2008;233:507-21. DOI: https://doi.org/10.3181/0710-MR-287
Chen WC, Wang CY, Hung YH, Weng TY, Yen MC, Lai MD. Systematic Analysis of gene expression alterations and clinical outcomes for long-chain acyl-coenzyme A synthetase family in cancer. Plos One 2016;11:e155660. DOI: https://doi.org/10.1371/journal.pone.0155660
Hartmann F, Sparla D, Tute E, Tamm M, Schneider U, Jeon MK, et al. Low acyl-CoA synthetase 5 expression in colorectal carcinomas is prognostic for early tumour recurrence. Pathol Res Pract 2017;213:261-6. DOI: https://doi.org/10.1016/j.prp.2016.09.002
Wit M, Trujillo-Viera J, Strohmeyer A, Klingenspor M, Hankir M, Sumara G. When fat meets the gut-focus on intestinal lipid handling in metabolic health and disease. Embo Mol Med 2022;14:e14742. DOI: https://doi.org/10.15252/emmm.202114742
Hsu FF. Mass spectrometry-based shotgun lipidomics - a critical review from the technical point of view. Anal Bioanal Chem 2018;410:6387-409. DOI: https://doi.org/10.1007/s00216-018-1252-y
Chen Y, Ma Z, Shen X, Li L, Zhong J, Min LS, et al. Serum lipidomics profiling to identify biomarkers for non-small cell lung cancer. Biomed Res Int 2018;2018:5276240. DOI: https://doi.org/10.1155/2018/5276240
Ros-Mazurczyk M, Jelonek K, Marczyk M, Binczyk F, Pietrowska M, Polanska J, et al. Serum lipid profile discriminates patients with early lung cancer from healthy controls. Lung Cancer 2017;112:69-74. DOI: https://doi.org/10.1016/j.lungcan.2017.07.036
Liu R, Cao K, Tang Y, Liu J, Li J, Chen J, et al. C16:0 ceramide effect on melanoma malignant behavior and glycolysis depends on its intracellular or exogenous location. Am J Transl Res 2020;12:1123-35.
Lin L, Ding Y, Wang Y, Wang Z, Yin X, Yan G, et al. Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology 2017;66:432-48. DOI: https://doi.org/10.1002/hep.29033
Diebels I, Van Schil P. Diagnosis and treatment of non-small cell lung cancer: current advances and challenges. J Thorac Dis 2022;14:1753-7. DOI: https://doi.org/10.21037/jtd-22-364
Min L, Zhu T, Lv B, An T, Zhang Q, Shang Y, et al. Exosomal LncRNA RP5-977B1 as a novel minimally invasive biomarker for diagnosis and prognosis in non-small cell lung cancer. Int J Clin Oncol 2022;27:1013-24. DOI: https://doi.org/10.1007/s10147-022-02129-5
Guo L, Li L, Xu Z, Meng F, Guo H, Liu P, et al. Metabolic network-based identification of plasma markers for non-small cell lung cancer. Anal Bioanal Chem 2021;413:7421-30. DOI: https://doi.org/10.1007/s00216-021-03699-5
Wang J, Zhang L, Wang C, Chen Y, Sui X. LINC00313/miR-4429 axis provides novel biomarkers for the diagnosis and prognosis of non-small cell lung cancer. Acta Biochim Pol 2022;69:343-8. DOI: https://doi.org/10.18388/abp.2020_5794
Fatima S, Hu X, Gong RH, Huang C, Chen M, Wong H, et al. Palmitic acid is an intracellular signaling molecule involved in disease development. Cell Mol Life Sci 2019;76:2547-57. DOI: https://doi.org/10.1007/s00018-019-03092-7
Bai D, Wu Y, Deol P, Nobumori Y, Zhou Q, Sladek FM, et al. Palmitic acid negatively regulates tumor suppressor PTEN through T366 phosphorylation and protein degradation. Cancer Lett 2021;496:127-33. DOI: https://doi.org/10.1016/j.canlet.2020.10.007
Li J, Fan Y, Zhang Y, Liu Y, Yu Y, Ma M. Resveratrol induces autophagy and apoptosis in non-small-cell lung cancer cells by activating the NGFR-AMPK-mTOR pathway. Nutrients 2022;14:2413. DOI: https://doi.org/10.3390/nu14122413
Tang G, Zeng Z, Sun W, Li S, You C, Tang F, et al. Small nucleolar RNA 71A promotes lung cancer cell proliferation, migration and invasion via MAPK/ERK pathway. J Cancer 2019;10:2261-75. DOI: https://doi.org/10.7150/jca.31077

Ethics Approval

this study was approved by the Animal Ethics Committee of Ningbo University (No. 2019-107)

Supporting Agencies

Natural Science Foundation of Zhejiang Province, Medical and Health Research Project of Zhejiang Province, Ningbo Key Discipline Construction Project , Ningbo Natural Science Foundation

How to Cite

Lv, J., Yanting, W., & Wei, S. (2023). Regulatory roles of ACSL5 in the anti-tumor function of palmitic acid (C16:0) <em>via</em> the ERK signaling pathway. European Journal of Histochemistry, 67(4). https://doi.org/10.4081/ejh.2023.3867
Copyright (c) 2023 The Author(s) Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.