近日，美国南卡罗来纳医科大学教授Philip H Howe及其团队的研究认为Fam3C改变三阴性乳腺癌的高尔基体形态和功能。该研究于2025年11月17日发表于国际一流学术期刊《分子细胞生物学报》杂志上。

课题组研究人员建立了Fam3C对三阴性乳腺癌患者的影响，以及自发乳腺癌肿瘤进展的基因工程小鼠模型。虽然Fam3C是一种已知的分泌蛋白，但该研究组发现它在高尔基体中保留是通过在其信号肽和前肽被加工和去除之前将其信号肽锚定在膜上。Fam3C保留在高尔基体中，影响细胞器的整体形态及其生物学功能，包括蛋白质分泌和侵袭电位的改变。扩大他们对EMT背后的生物学机制的了解将有助于开发专门针对三阴性乳腺癌中转移潜力增加的细胞的治疗方法。

据介绍，Fam3C，也被称为白细胞介素样EMT诱导剂（ILEI），是上皮细胞向间质转化和乳腺癌干细胞表型的公认调节剂。多种肿瘤细胞模型和原位动物模型实验已经证实Fam3C在肿瘤进展和转移中的作用。

附：英文原文

Title: Fam3C alters Golgi apparatus morphology and function in triple negative breast cancer

Author: Dalton, Annamarie C, Rochel, Elisabeth R M, Streitfeld, William S, Fréreux, Cécile, Howley, Breege V, Howe, Philip H

Issue&Volume: 2025-11-17

Abstract: Fam3C, also known as Interleukin-like EMT inducer (ILEI), is an established regulator of the epithelial to mesenchymal transition and breast cancer stem cell phenotypes. Multiple cancer cell models and orthotopic animal model experiments have demonstrated a role for Fam3C in tumor progression and metastasis. Here, we establish Fam3C’s impact on triple negative breast cancer patients and genetically engineered mouse models of spontaneous breast cancer tumor progression. Though Fam3C is a known secreted protein, we discovered its retention in the Golgi apparatus through anchoring of its signal peptide into the membrane before its signal peptide and pro-peptide are processed and removed. While retained in the Golgi apparatus, Fam3C affects the overall morphology of the organelle and its biological functions, including alterations in protein secretion and invasive potential. Expanding our knowledge of the biological mechanisms behind EMT will help develop therapies to specifically target cells with increased metastatic potential in triple negative breast cancer.

DOI: 10.1093/jmcb/mjaf042

Source: https://dx.doi.org/10.1093/jmcb/mjaf042