SLC7A11 promotes EMT and metastasis in invasive pituitary neuroendocrine tumors by activating the PI3K/AKT signaling pathway.

Abstract

Invasive pituitary neuroendocrine tumors (PitNETs) are the most prevalent types of intracranial and neuroendocrine tumors. Their aggressive growth and difficulty in complete resection result in a high recurrence rate. Cystine transporter solute carrier family 7 member 11 (SLC7A11) is overexpressed in various cancers, which contributes to tumor growth, progression, and metastasis by promoting cystine uptake and glutathione biosynthesis. We identified SLC7A11 as an invasive biomarker based on three Gene Expression Omnibus cohorts. This study aimed to investigate the role of SLC7A11 in invasive PitNETs. Cell proliferation was assessed using CCK-8 and colony formation assays, while cell apoptosis was estimated with flow cytometry. Wound healing assays and transwell assays were utilized to evaluate migration and invasion ability. Our findings demonstrated that SLC7A11 was markedly upregulated in invasive PitNETs, and was associated with the invasiveness of PitNETs. Knockdown of SLC7A11 could largely suppress tumor cell proliferation, migration, and invasion, while inducing apoptosis. Furthermore, SLC7A11 depletion was implicated in regulating epithelial-mesenchymal transition and inactivating the PI3K/AKT signaling pathway. These insights suggest SLC7A11 as a potential therapeutic target for invasive PitNETs.