由于对现有放疗、化疗和靶向治疗不敏感，三阴性乳腺癌（TNBC）仍然是一个需要克服的巨大挑战。越来越多的证据表明，TNBC 中存在异常的 Wnt/β-catenin 通路激活，但管腔或 HER2 乳腺癌中则不然，lncRNA 在多种癌症中发挥着关键作用。通过对 TNBC 组织的激活和失活 wnt/β-catenin 通路进行 lncRNA 微阵列分析，与失活组。使用 RIP-seq 比较 β-catenin 和 IgG 组，其中 lnc-WAL 可以与 β-catenin 相互作用。临床上，TNBC 肿瘤组织中 lnc-WAL 的增加与较短的生存期相关。 lnc-WAL 促进 EMT、乳腺癌干细胞 (BCSC) 和 TNBC 细胞的增殖、迁移和侵袭。从机制上讲，lnc-WAL 通过 Axin 介导的丝氨酸 45 磷酸化抑制 β-catenin 蛋白降解。随后，β-catenin 在细胞核中积累并激活靶基因。重要的是，wnt/β-catenin 通路激活刺激了 lnc-WAL 的转录。这些结果表明lnc-WAL/Axin/β-catenin在TNBC的恶性进展中起主要调节作用。我们的研究结果提供了重要的临床转化证据，表明 lnc-WAL 可能是 TNBC 的潜在治疗靶点。意义：lnc-WAL 与 Wnt/β-catenin 通路之间的正反馈促进 TNBC 进展，lnc-WAL 可能成为 TNBC 患者的潜在预后标志物。

Because of its insensitivity to existing radiotherapy, namely chemotherapy and targeted treatments, triple-negative breast cancer (TNBC) remains a great challenge to overcome. Increasing 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 upregulated lncRNA in wnt/β-catenin pathway activation compared with the inactivation group. RIP-seq was used to compare the β-catenin and IgG groups, where lnc-WAL could interact with β-catenin. Clinically, increased lnc-WAL in TNBC tumor tissue was associated with shorter survival. lnc-WAL promoted EMT, the proliferation, migration and invasion of breast cancer stem cells (BCSCs), and TNBC cells. Mechanistically, lnc-WAL inhibited β-catenin protein degradation via Axin-mediated phosphorylation at serine 45. Subsequently, β-catenin accumulated in the nucleus 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 may be a potential therapeutic target against TNBC. Implications: The positive feedback between lnc-WAL and the Wnt/β-catenin pathway promotes TNBC progression, and lnc-WAL could be a potential prognostic marker for TNBC patients.