Institut Curie - Centre de Recherche, PSL Research University, Membrane Dynamics and Mechanics of Intracellular Signaling team, 75248, Paris, cedex 05, France.
Institut National de la Santé et de la Recherche Médicale (INSERM), U1143, Paris, France.
Sci Rep. 2020 May 14;10(1):7998. doi: 10.1038/s41598-020-65054-5.
EHD2 is a mechanotransducing ATPase localized in caveolae invaginations at the plasma membrane. EHD2 has recently been associated with several human cancers, however the significance of EHD2 transcript levels in cancer prognosis remains debated. Breast cancer is the most commonly occurring cancer in women and prognosis is variable depending on the subtypes. Triple negative breast cancer (TNBC) often has a poor therapeutic response. The aim of this study was to assess the prognostic significance of EHD2 transcripts and protein expression levels in breast carcinomas. We found that low EHD2 levels were associated with enhanced proliferation, migration and invasion of TNBC cells. EHD2 expression was significantly reduced in TNBC tissues and the loss of EHD2 led to higher expression of the pro-tumoral cytokine IL-8. In apparent contradiction with in vitro data, multivariate analysis of two independent cohorts of breast cancer patients revealed that low EHD2 was in fact associated with good prognosis in the highly proliferative TNBC subtype. Accordingly, TNBC low EHD2 expressers were found to benefit the most from chemotherapy when compared to all subtypes of breast cancers. Our study validates EHD2 expression level as an independent prognostic factor of metastasis-free survival and as a new predictive marker of chemotherapy efficacy in TNBC patients.
EHD2 是一种机械转导的 ATP 酶，位于质膜凹陷的小窝内。EHD2 最近与几种人类癌症相关联，但是 EHD2 转录本水平在癌症预后中的意义仍存在争议。乳腺癌是女性中最常见的癌症，预后因亚型而异。三阴性乳腺癌（TNBC）通常对治疗反应不佳。本研究旨在评估 EHD2 转录本和蛋白表达水平在乳腺癌中的预后意义。我们发现 EHD2 水平低与 TNBC 细胞增殖、迁移和侵袭增强有关。EHD2 在 TNBC 组织中表达显著降低，EHD2 的缺失导致促肿瘤细胞因子 IL-8 的表达升高。与体外数据明显矛盾的是，对两个独立的乳腺癌患者队列的多变量分析表明，低 EHD2 实际上与高度增殖性 TNBC 亚型的良好预后相关。因此，与所有乳腺癌亚型相比，TNBC 低 EHD2 表达者在化疗中获益最多。我们的研究验证了 EHD2 表达水平作为无转移生存的独立预后因素，以及 TNBC 患者化疗疗效的新预测标志物。
