文章：

MUC1驱动透明细胞肾癌的进展与化疗耐药性

MUC1 Drives the Progression and Chemoresistance of Clear Cell Renal Carcinomas

原文发布日期：17 January 2024

DOI: 10.3390/cancers16020391

类型: Article

开放获取: 是

英文摘要：

While the transmembrane glycoprotein mucin 1 (MUC1) is clustered at the apical borders of normal epithelial cells, with transformation and loss of polarity, MUC1 is found at high levels in the cytosol and is uniformly distributed over the entire surface of carcinoma cells, where it can promote tumor progression and adversely affects the response to therapy. Clear cell renal cell carcinoma (ccRCC), the main histotype of kidney cancer, is typically highly resistant to conventional and targeted therapies for reasons that remain largely unknown. In this context, we investigated whether MUC1 also plays a pivotal role in the cellular and molecular events driving ccRCC progression and chemoresistance. We showed, using loss- and gain-of-function approaches in ccRCC-derived cell lines, that MUC1 not only influences tumor progression but also induces a multi-drug-resistant profile reminiscent of the activation of ABC drug efflux transporters. Overall, our results suggest that targeting MUC1 may represent a novel therapeutic approach to limit ccRCC progression and improve drug sensitivity.

摘要翻译： 

跨膜糖蛋白粘蛋白1（MUC1）在正常上皮细胞中通常聚集于细胞顶端边界，而在细胞发生转化并失去极性后，MUC1在癌细胞胞质中呈现高表达状态，并均匀分布于整个细胞表面，从而促进肿瘤进展并对治疗反应产生负面影响。透明细胞肾细胞癌（ccRCC）作为肾癌的主要组织亚型，通常对常规及靶向治疗表现出高度耐药性，其具体机制尚不明确。在此背景下，本研究探讨了MUC1是否在驱动ccRCC进展及化疗耐药的细胞与分子事件中发挥关键作用。通过在ccRCC来源细胞系中采用功能缺失与功能获得策略，我们发现MUC1不仅影响肿瘤进展，还能诱导产生类似于ABC药物外排转运蛋白激活的多药耐药表型。总体而言，本研究结果表明靶向MUC1可能成为抑制ccRCC进展并提升药物敏感性的新型治疗策略。

原文链接：

MUC1 Drives the Progression and Chemoresistance of Clear Cell Renal Carcinomas