9-Hexadecenoic acid inhibits the aggressiveness of gastric cancer via targeting PTPN1/FTH1 signaling

9-Hexadecenoic acid (9-HA) possesses anti-tumor properties. However, the effects of 9-HA on gastric cancer are scarcely reported. The present study aimed to investigate the effects of 9-HA on gastric cancer. mRNA levels were detected by reverse transcription quantitative PCR. Protein expression was detected by western blot. Cell behaviors were analyzed using Cell Counting Kit-8, colony formation, transwell, and propidium iodide staining assays. Co-localization of PTPN1 and FTH1 was determined using fluorescence in situ hybridization assay. In vivo assay was conducted to further verify the effects of 9-HA on gastric cancer. 9-HA suppressed the malignant behavior of gastric cancer. Moreover, 9-HA promoted iron-overload-dependent ferroptosis of gastric cancer in vivo and in vitro. Traditional Chinese medicine systems pharmacology predicted that 9-HA could target PTPN1, which was upregulated in gastric cancer cells. PTPN1-mediated phosphorylation of FTH1 contributed to the latter degradation. Overexpressed PTPN1 alleviated the effects of 9-HA, promoting the aggressiveness of gastric cancer and suppressing tumor cell ferroptosis. Interestingly, overexpressed PTPN1 antagonized the effects of 9-HA, promoted tumor growth, and inhibited the ferroptosis of gastric cancer. In summary, 9-HA-mediated downregulation of PTPN1 drives ferroptosis and inhibit the aggressiveness of gastric cancer. Thence, 9-HA may be an alternative strategy for gastric cancer.