@Article{or.2026.077171,
AUTHOR = {Chunhui Tian, Weipin Xie, Wen Li, Huaiyu Gu, Xuebao Liu, Busheng Tong, Yehai Liu, Huaiyuan Zong},
TITLE = {SLC16A1 Activates the STAT3/SLC7A11 Pathway to Mediate Ferroptosis Resistance and Tumor Progression in Head and Neck Squamous Cell Carcinoma},
JOURNAL = {Oncology Research},
VOLUME = {34},
YEAR = {2026},
NUMBER = {5},
PAGES = {--},
URL = {http://www.techscience.com/or/v34n5/67077},
ISSN = {1555-3906},
ABSTRACT = { <b>Background:</b> In head and neck squamous cell carcinoma (HNSCC), solute carrier family 16 member 1 (SLC16A1) is associated with tumor advancement and reduced sensitivity to ferroptosis, yet the molecular basis of these effects remains unclear. This study seeks to uncover how SLC16A1 contributes to HNSCC tumorigenesis. <b>Methods:</b> To elucidate how SLC16A1 drives HNSCC progression via ferroptosis resistance, we performed RNA sequencing on SLC16A1-knockdown HNSCC cells and controls, followed by functional validation. We next systematically assessed the role of the candidate molecule solute carrier family 7 member 11 (SLC7A11) in HNSCC progression and resistance to ferroptosis using loss- and gain-of-function experiments <i>in vitro</i> and xenograft-based assays <i>in vivo</i>. Finally, we applied RNA interference and validated expression changes by quantitative real-time polymerase chain reaction and immunoblotting to map the signaling pathway by which SLC16A1 controls SLC7A11 expression. <b>Results:</b> Integrated RNA sequencing and functional assays identified SLC7A11 as a key downstream effector of SLC16A1. SLC7A11 mediates SLC16A1-driven tumor cell proliferation, ferroptosis resistance, and tumorigenesis. Mechanistically, SLC16A1 activates signal transducer and activator of transcription 3 (STAT3) to transcriptionally upregulate SLC7A11 expression. <b>Conclusion:</b> Our study defines a novel SLC16A1–STAT3–SLC7A11 signaling axis that promotes HNSCC progression by conferring robust resistance to ferroptosis. This axis may be leveraged as a therapeutic target to mitigate treatment resistance.},
DOI = {10.32604/or.2026.077171}
}