BACKGROUND Breast cancer is the leading cause of cancer-related death in women worldwide. Metastatic disease remains the primary cause of death in patients with breast cancer. Basal-like breast cancer (BLBC) is associated with aggressive behavior, stem-like phenotype, high histological grade, poor clinical features, and high rates of recurrences and/or metastasis. However, the mechanism of BLBC phenotype shaping remains obscure. METHODS Seventeen normal breast/breast cancer cell lines were used for evaluating the breast cancer subtype-markers, WNT targets and constitutive components, and epithelial mesenchymal transition (EMT) markers analysis by western blot. One hundred and twenty formalin-fixed breast cancer tissues were used for immunohistochemistry (IHC) staining. Nine online platforms (cBioPortal, CCLE, GEPIA, etc.) were used for related analyses. RESULTS We identified Wnt5b as a key regulatory factor that governs the phenotype of BLBC by activating canonical and non-canonical WNT signaling. Wnt5b exhibited basal-like specificity in cells and clinical samples both at the mRNA and protein levels and also showed good correlation with basal-like phenotype at the mRNA level. Besides, Wnt5b was also a promising therapeutic target for LGK-974 treatment. In addition, we identified that CK1α was expressed at low levels in BLBC and that the activation of CK1α by pyrvinium was an alternative strategy for BLBC treatment. CONCLUSIONS Wnt5b is not only a diagnostic biomarker but also a potential therapeutic target of BLBC.

中文翻译：

---

WNT5B通过激活WNT信号传导控制基底样乳腺癌的表型。

背景技术乳腺癌是全世界女性与癌症相关的死亡的主要原因。转移性疾病仍然是乳腺癌患者死亡的主要原因。基底样乳腺癌（BLBC）与攻击行为，茎样表型，组织学等级高，临床特征差以及复发和/或转移率高有关。但是，BLBC表型塑造的机制仍然不清楚。方法采用17个正常的乳腺癌/乳腺癌细胞系，通过western blot评估乳腺癌亚型标志物，WNT靶标和组成成分，以及上皮间质转化（EMT）标志物的分析。将一百二十个福尔马林固定的乳腺癌组织用于免疫组织化学（IHC）染色。九个在线平台（cBioPortal，CCLE，GEPIA等））用于相关分析。结果我们确定Wnt5b是通过激活规范性和非规范性WNT信号来控制BLBC表型的关键调节因子。Wnt5b在细胞和临床样品中均在mRNA和蛋白质水平上表现出基底样特异性，并且在mRNA水平上也与基底样表型表现出良好的相关性。此外，Wnt5b也是LGK-974治疗的有希望的治疗靶标。此外，我们发现CK1α在BLBC中的表达水平较低，而pyrvinium激活CK1α是BLBC治疗的另一种策略。结论Wnt5b不仅是诊断性生物标志物，而且还是BLBC的潜在治疗靶标。结果我们确定Wnt5b是通过激活规范性和非规范性WNT信号来控制BLBC表型的关键调节因子。Wnt5b在细胞和临床样品中均在mRNA和蛋白质水平上表现出基底样特异性，并且在mRNA水平上也与基底样表型表现出良好的相关性。此外，Wnt5b也是LGK-974治疗的有希望的治疗靶标。此外，我们发现CK1α在BLBC中的表达水平较低，而pyrvinium激活CK1α是BLBC治疗的另一种策略。结论Wnt5b不仅是诊断性生物标志物，而且还是BLBC的潜在治疗靶标。结果我们确定Wnt5b是通过激活规范性和非规范性WNT信号来控制BLBC表型的关键调节因子。Wnt5b在细胞和临床样品中均在mRNA和蛋白质水平上表现出基底样表型特异性，并且在mRNA水平上也与基底样表型表现出良好的相关性。此外，Wnt5b也是LGK-974治疗的有希望的治疗靶标。此外，我们发现CK1α在BLBC中的表达水平较低，而pyrvinium激活CK1α是BLBC治疗的另一种策略。结论Wnt5b不仅是诊断性生物标志物，而且还是BLBC的潜在治疗靶标。Wnt5b在细胞和临床样品中均在mRNA和蛋白质水平上表现出基底样特异性，并且在mRNA水平上也与基底样表型表现出良好的相关性。此外，Wnt5b也是LGK-974治疗的有希望的治疗靶标。此外，我们发现CK1α在BLBC中的表达水平较低，而pyrvinium激活CK1α是BLBC治疗的另一种策略。结论Wnt5b不仅是诊断性生物标志物，而且还是BLBC的潜在治疗靶标。Wnt5b在细胞和临床样品中均在mRNA和蛋白质水平上表现出基底样特异性，并且在mRNA水平上也与基底样表型表现出良好的相关性。此外，Wnt5b也是LGK-974治疗的有希望的治疗靶标。此外，我们发现CK1α在BLBC中的表达水平较低，而pyrvinium激活CK1α是BLBC治疗的另一种策略。结论Wnt5b不仅是诊断性生物标志物，而且还是BLBC的潜在治疗靶标。