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

Author:

Ma Yunxia1ORCID,Nenkov Miljana1ORCID,Berndt Alexander1,Abubrig Mohamed1,Schmidt Martin2ORCID,Sandhaus Tim3,Huber Otmar2ORCID,Clement Joachim H.4ORCID,Lang Susanne M.5,Chen Yuan1ORCID,Gaßler Nikolaus1

Affiliation:

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

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.

Funder

University Hospital Jena, Germany

Publisher

MDPI AG

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