Cancers | Free Full-Text | The Diagnostic Value of ACSL1, ACSL4, and ACSL5 and the Clinical Potential of an ACSL Inhibitor in Non-Small-Cell Lung Cancer
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Open AccessArticle
by
Yunxia Ma
Miljana Nenkov
Alexander Berndt
Mohamed Abubrig
Martin Schmidt
Tim Sandhaus
Otmar Huber
Joachim H. H. Clement
Susanne M. M. Lang
Yuan Chen
Nikolaus Gaßler
Yunxia Ma
1
,
Miljana Nenkov
1,
Alexander Berndt
1,
Mohamed Abubrig
1,
Martin Schmidt
2,
Tim Sandhaus
3,
Otmar Huber
2,
Joachim H. H. Clement
4,
Susanne M. M. Lang
Yuan Chen
Nikolaus Gaßler
1
Section Pathology of the Institute of Forensic Medicine, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany
2
Institute of Biochemistry II, Jena University Hospital, Friedrich Schiller University Jena, Nonnenplan 2, 07747 Jena, Germany
3
Clinic of Cardiothoracic Surgery, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany
4
Department of Hematology and Medical Oncology, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany
5
Department of Internal Medicine V, Jena University Hospital, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany
*
Authors to whom correspondence should be addressed.
Cancers 2024, 16(6), 1170; https://doi.org/10.3390/cancers16061170 (registering DOI)
Submission received: 26 February 2024
/
Revised: 11 March 2024
/
Accepted: 15 March 2024
/
Published: 16 March 2024
Simple Summary
Long-chain Acyl-CoA synthetase (ACSL) family members are involved in long-chain fatty acid activation, a crucial step for cells to utilize fatty acids (FAs) in the regulation of FA homeostasis. Cancer cells utilize the limited environmental FAs via the dysregulation of ACSL isoforms to adapt to an altered lipid metabolism. Dysregulated ACSLs are associated with either cancer promotion or inhibition, dependent on the cellular context. The role of ACSLs in different cancer types has not yet been fully elucidated, and, particularly, their role in lung cancer is unclear. In this study, we analyzed the expression pattern of ACSLs, evaluated their diagnostic values, and explored the therapeutic potential of the ACSL inhibitor Triacsin C in human lung cancer cells.
Abstract
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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MDPI and ACS Style
Ma, Y.; Nenkov, M.; Berndt, A.; Abubrig, M.; Schmidt, M.; Sandhaus, T.; Huber, O.; Clement, J.H.H.; Lang, S.M.M.; Chen, Y.;
et al. The Diagnostic Value of ACSL1, ACSL4, and ACSL5 and the Clinical Potential of an ACSL Inhibitor in Non-Small-Cell Lung Cancer. Cancers 2024, 16, 1170.
https://doi.org/10.3390/cancers16061170
AMA Style
Ma Y, Nenkov M, Berndt A, Abubrig M, Schmidt M, Sandhaus T, Huber O, Clement JHH, Lang SMM, Chen Y,
et al. The Diagnostic Value of ACSL1, ACSL4, and ACSL5 and the Clinical Potential of an ACSL Inhibitor in Non-Small-Cell Lung Cancer. Cancers. 2024; 16(6):1170.
https://doi.org/10.3390/cancers16061170
Chicago/Turabian Style
Ma, Yunxia, Miljana Nenkov, Alexander Berndt, Mohamed Abubrig, Martin Schmidt, Tim Sandhaus, Otmar Huber, Joachim H. H. Clement, Susanne M. M. Lang, Yuan Chen,
and et al. 2024. “The Diagnostic Value of ACSL1, ACSL4, and ACSL5 and the Clinical Potential of an ACSL Inhibitor in Non-Small-Cell Lung Cancer” Cancers 16, no. 6: 1170.
https://doi.org/10.3390/cancers16061170
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