乳腺癌（BC）中的内腔亚型是乳腺癌的主要亚型，具有长期复发和死亡风险。了解内腔乳腺癌的肿瘤发生分子机制将改善这一大型患者亚组的预后。已报告SPDEF在乳腺癌中发生失调。然而，SPDEF在内腔乳腺癌中的生物学功能和潜在的分子机制仍然大部分未知。本研究旨在阐明SPDEF在乳腺癌亚型特异功能中的潜在作用，特别是在内腔亚型中。通过生物信息学分析评估了SPDEF在内腔乳腺癌患者中的表达和临床病理特征。进行了体外和体内实验，以研究SPDEF在内腔乳腺癌中的致癌功能和干细胞性维持。进行染色质免疫沉淀（ChIP）和双荧光素酶报告基因检测，以确定SPDEF对GALNT7的转录调控。进一步通过酶联免疫吸附测定法（ELISA）检测内腔乳腺癌患者血清中的GALNT7水平。SPDEF在内腔乳腺癌中显著上调，与肿瘤进展和预后不良呈正相关。此外，我们证实SPDEF在内腔乳腺癌细胞的增殖、迁移、侵袭和干细胞性方面具有促进作用，以及在体内的肿瘤形成能力。就机制而言，我们证明了SPDEF对内腔乳腺癌进展和干细胞性的刺激作用，这是通过其直接转录靶基因GALNT7介导的。临床上，我们验证了GALNT7可用作非侵入性诊断标志物。值得注意的是，血清GALNT7和传统肿瘤标志物的联合检测可以提高诊断准确性，因此对内腔乳腺癌的早期诊断非常重要。我们的研究揭示了一种新的机制，即SPDEF通过直接结合到其启动子上，转录激活GALNT7，从而促进细胞增殖、迁移、干细胞性，并导致内腔乳腺癌的肿瘤发生和预后不良。© 2023. 作者。

Luminal breast cancer (BC) is the predominant subtype of breast cancer with a sustained risk of late recurrence and death. Understanding the molecular mechanisms for the oncogenesis of luminal BC would improve the prognosis for this large subset of patients. SPDEF was reported to be dysregulated in breast cancers. However, the biological functions and underlying molecular mechanism of SPDEF in luminal BC remains largely unknown. The aim of the present study was to elucidate the potential roles of SPDEF underlying subtype-specific functions in BC, especially in luminal subtypes.The expressions and clinicopathological characteristics of SPDEF in luminal BC patients were evaluated bioinformatically. In vitro and in vivo assays were performed to investigate the oncogenic function and stemness maintenance of SPDEF in luminal BC. Chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays were conducted to determine the transcription regulation of GALNT7 by SPDEF. GALNT7 levels in serum from luminal BC patients were further detected by enzyme-linked immunosorbent assay (ELISA).SPDEF is markedly upregulated in luminal BC and positively associated with tumor progression and poor prognosis. Furthermore, we confirmed that SPDEF enhanced the proliferation, migration, invasion and stemness of luminal BC cells in vitro as well the tumorigenicity in vivo. Mechanistically, we demonstrated the stimulative effect of SPDEF on the progression and stemness of luminal BC, which is mediated by its directly transcriptional target GALNT7. Clinically, we verified that the GALNT7 can be used as a noninvasive diagnostic marker. Noteworthy, the combined detection of serum GALNT7 and traditional tumor markers can enhance diagnostic accuracy thus is of vital importance in the early diagnosis of luminal BC.Our study reveals a novel mechanism by which SPDEF transcriptionally activates GALNT7 via directly binding to its promoter to promote cell proliferation, motility and stemness, and led to luminal BC tumorigenesis and poor prognosis.© 2023. The Author(s).