@Article{or.2026.077693,
AUTHOR = {Ching-Chun Ho, Yen-Cheng Chen, Wei-Liang Lean, Wen-Sheng Wu},
TITLE = {Extracellular Signal-Regulated Kinase and Reactive Oxygen Species Regulate PD-L1 to Promote Migration and Proliferation of Triple-Negative Breast Cancer MDA-MB-231 Cells},
JOURNAL = {Oncology Research},
VOLUME = {},
YEAR = {},
NUMBER = {},
PAGES = {{pages}},
URL = {http://www.techscience.com/or/online/detail/27270},
ISSN = {1555-3906},
ABSTRACT = {<b>Objectives:</b> Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer. Mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), as well as protein kinase B (AKT), are potential therapeutic targets for TNBC. Programmed death-ligand 1 (PD-L1) is implicated in TNBC progression and is associated with AKT and ERK signaling pathways. In addition, reactive oxygen species (ROS) act upstream of MAPK/AKT and PD-L1. In this study, we aimed to clarify the role of PD-L1 in TNBC progression and to delineate the underlying signaling mechanisms. <b>Methods:</b> Western blotting and reverse transcription–polymerase chain reaction were used to analyze protein and mRNA levels, respectively. Transwell migration and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assays were used to assess cell migration and proliferation, respectively. <b>Results:</b> The ERK inhibitor (PD98059) suppressed MDA-MB-231 cell migration but not proliferation, whereas PD-L1 siRNA and the ROS scavenger dithiothreitol (DTT) reduced both cell migration and proliferation. However, PD-L1 siRNA and DTT did not reduce the activities of ERK, JNK, or AKT. Whereas PD98059 and DTT suppressed PD-L1 protein expression, PD-L1 mRNA expression could be reduced by DTT only. Taken together, ROS and ERK may activate different pathways to regulate PD-L1 expression and MDA-MB-231 cell progression. Consistently, DTT combined with PD98059 additively inhibited MDA-MB-231 cell migration. Similar observations were noted in another TNBC cell line, Hs578T, which exhibits motility, but not in MDA-MB-453 cells, which lack motility. <b>Conclusion:</b> Since PD-L1 appears to function downstream of ERK and ROS and is required for TNBC progression, co-targeting both ERK and ROS signaling pathways may represent a promising therapeutic strategy for TNBC.},
DOI = {10.32604/or.2026.077693}
}