Hippo pathway effectors YAP, TAZ and TEAD are associated with EMT master regulators ZEB, Snail and with aggressive phenotype in phyllodes breast tumors

IF 2.9 4区医学 Q2 PATHOLOGY Pathology, research and practice Pub Date : 2024-08-15 DOI:10.1016/j.prp.2024.155551

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Abstract

Background

Phyllodes tumors (PTs) of the breast are uncommon fibroepithelial neoplasms that tend to recur locally and may have metastatic potential. Their pathogenesis is poorly understood. Hippo signaling pathway plays an essential role in organ size control, tumor suppression, tissue regeneration and stem cell self-renewal. Hippo signaling dysfunction has been implicated in cancer. Recent evidence suggests that there is cross-talk between the Hippo signaling key proteins YAP/TAZ and the epithelial-mesenchymal transition (EMT) master regulators Snail and ZEB. In this study we aimed to investigate the expression of Hippo signaling pathway components and EMT regulators in PTs, in relation to tumor grade.

Methods

Expression of Hippo signaling effector proteins YAP, TAZ and their DNA binding partner TEAD was evaluated by immunohistochemistry in paraffin-embedded tissue specimens from 86 human phyllodes breast tumors (45 benign, 21 borderline, 20 malignant), in comparison with tumor grade and with the expression of EMT-related transcription factors ZEB and Snail.

Results

Nuclear immunopositivity for YAP, TAZ and TEAD was detected in both stromal and epithelial cells in PTs and was significantly higher in high grade tumors. Interestingly, there was a significant correlation between the expression of YAP, TAZ, TEAD and the expression of ZEB and SNAIL.

Conclusions

Our results originally implicate Hippo signaling pathway in PTs pathogenesis and suggest that an interaction between Hippo signaling key components and EMT regulators may promote the malignant features of PTs.

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Hippo通路效应因子YAP、TAZ和TEAD与EMT主调控因子ZEB和Snail有关，并与植物乳腺肿瘤的侵袭性表型有关

背景乳腺良性肿瘤（PTs）是一种不常见的纤维上皮肿瘤，易局部复发，并有转移的可能。人们对其发病机制知之甚少。Hippo信号通路在器官大小控制、肿瘤抑制、组织再生和干细胞自我更新中发挥着重要作用。Hippo 信号传导功能障碍与癌症有关。最近的证据表明，Hippo 信号关键蛋白 YAP/TAZ 与上皮-间质转化（EMT）主调节因子 Snail 和 ZEB 之间存在交叉作用。方法通过免疫组织化学方法评估86例人类乳腺鳞状上皮细胞瘤（45例良性，21例边缘性，20例恶性）石蜡包埋组织标本中Hippo信号转导效应蛋白YAP、TAZ及其DNA结合伙伴TEAD的表达，并与肿瘤分级以及EMT相关转录因子ZEB和Snail的表达进行比较。结果在PT的基质细胞和上皮细胞中都检测到了YAP、TAZ和TEAD的核免疫阳性，在高级别肿瘤中明显更高。有趣的是，YAP、TAZ和TEAD的表达与ZEB和SNAIL的表达之间存在明显的相关性。结论我们的研究结果初步揭示了Hippo信号通路在PTs发病机制中的作用，并提示Hippo信号通路关键成分与EMT调控因子之间的相互作用可能会促进PTs恶性特征的形成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.