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Background: Long-chain acyl-CoA synthetase-4 (ACSL4) is involved in fatty acid metabolism, and aberrant ACSL4 expression could be either tumorigenic or tumor-suppressive in different tumor types. However, the function and clinical significance of ACSL4 in lung adenocarcinoma remain elusive. Results: ACSL4 was frequently downregulated in lung adenocarcinoma when analyzing both the TCGA database and the validation samples, and the lower ACSL4 expression was correlated with a worse prognosis. Using gene set enrichment analysis, we found that high ACSL4 expression was frequently associated with the oxidative stress pathway, especially ferroptosis-related proteins. In vitro functional studies showed that knockdown of ACSL4 increased tumor survival/invasiveness and inhibited ferroptosis, while ACSL4 overexpression exhibited the opposite effects. Moreover, high-fat treatment could also inhibit erastin-induced ferroptosis by affecting ACSL4 expression. The anti-tumor effects of ferroptosis inducers and the anti-ferroptosis effects of the high-fat diet were further validated using the mouse xenograft model. Conclusions: ACSL4 plays a tumor-suppressive role in lung adenocarcinoma by suppressing tumor survival/invasiveness and promoting ferroptosis. Our study provided a theoretical reference for the application of ferroptotic inducers and dietary guidance for lung adenocarcinoma patients. [ABSTRACT FROM AUTHOR]

In recent years, the morbidity rate resulting from numerous types of malignant tumor has increased annually, and the treatment of tumors has been attracting an increasing amount of attention. A number of recent studies have revealed that the water channel protein aquaporin-5 (AQP5) has become a major player in multiple types of cancer. AQP5 is abnormally expressed in a variety of tumor tissues or cells and has multiple effects on certain biological functions of tumors, such as regulating the proliferation, apoptosis and migration of tumor cells. It has been suggested that AQP5 may play an important role in the process of tumor development, opening up a new field of tumor research. The present review highlighted the structure of AQP5 and its role in tumor progression. Furthermore, the expression of AQP5 in different malignant neoplasms was summarized. In addition, the influence of not only drugs, but also different compounds on AQP5 were summarized. In conclusion, according to the findings in the present review, AQP5 has potential as a novel therapeutic target in human cancer, and other AQPs should be similarly investigated. [ABSTRACT FROM AUTHOR]