lncRNA-WAL Promotes Aggressiveness of Triple-Negative Breast Cancer via inducing β-Catenin nuclear translocation

Because of its insensitive to existing radiotherapy, chemotherapy and targeted treatments, Triple-negative breast cancer (TNBC) remains a great challenge to overcome. More and more evidence has indicated abnormal wnt/β-catenin pathway activation in TNBC but not luminal or her2+ breast cancer, and lncRNAs play a key role in a variety of cancers. Through lncRNA microarray profiling between Activated and inactivated Wnt/β-catenin pathway of TNBC tissues, lnc-WAL (Wnt/β-catenin associated lncRNA; WAL) was selected as the top up-regulated lncRNA in Wnt/β-catenin pathway activation compared with the inactivation group. RIP-seq was analyzed between β-catenin and IgG groups of, where lnc-WAL could interact with β-catenin. Clinically, increased lnc-WAL in the TNBC tumor tissue was associated with shorter survival. lnc-WAL promoted the EMT, the ability of breast cancer stem cells (BCSC), proliferation, migration and invasion of TNBC cells. Mechanistically, lnc-WAL inhibited β-catenin protein degradation via Axin-mediated phosphorylation at serine 45. Subsequently, β-catenin was accumulated in nuclear and activated the target genes. Importantly, Wnt/β-catenin pathway activation stimulated the transcription of lnc-WAL. These results pointed to a master regulatory role of lnc-WAL/Axin/β-catenin in the malignant progression of TNBC. Our findings provide important clinical translational evidence that lnc-WAL maybe as potential therapeutic target against TNBC.