乳腺癌中毛发角蛋白 81 截短亚型的异位表达改变生物物理特征,促进转移倾向。
Ectopic Expression of a Truncated Isoform of Hair Keratin 81 in Breast Cancer Alters Biophysical Characteristics to Promote Metastatic Propensity.
发表日期:2023 Nov 10
作者:
Diane S Kang, Aidan Moriarty, Yiru Jess Wang, Amal Thomas, Jia Hao, Bret A Unger, Remi Klotz, Shamim Ahmmed, Yonatan Amzaleg, Stuart Martin, Siva Vanapalli, Ke Xu, Andrew Smith, Keyue Shen, Min Yu
来源:
PHARMACOLOGY & THERAPEUTICS
摘要:
角蛋白是细胞结构和功能的组成部分。研究表明,与原发性肿瘤和患者来源的循环肿瘤细胞相比,乳腺癌中角蛋白 81 截短亚型 (tKRT81) 的异位表达在转移性病变中上调,并且与更具侵袭性的亚型相关。 tKRT81 与角蛋白 18 (KRT18) 发生物理相互作用,导致胞质角蛋白中间丝网络的变化和桥粒斑块的形成。这些结构变化与更软、更具弹性变形性的癌细胞相关,其具有增强的粘附和聚集能力,导致更大的体内肺转移负担。这项工作描述了 tKRT81 促进转移的新型生物力学机制,强调了肿瘤细胞生物物理特征的重要性。© 2023 作者。 《先进科学》由 Wiley-VCH GmbH 出版。
Keratins are an integral part of cell structure and function. Here, it is shown that ectopic expression of a truncated isoform of keratin 81 (tKRT81) in breast cancer is upregulated in metastatic lesions compared to primary tumors and patient-derived circulating tumor cells, and is associated with more aggressive subtypes. tKRT81 physically interacts with keratin 18 (KRT18) and leads to changes in the cytosolic keratin intermediate filament network and desmosomal plaque formation. These structural changes are associated with a softer, more elastically deformable cancer cell with enhanced adhesion and clustering ability leading to greater in vivo lung metastatic burden. This work describes a novel biomechanical mechanism by which tKRT81 promotes metastasis, highlighting the importance of the biophysical characteristics of tumor cells.© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.