Polyploidal giant cancer cells (PGCCs) are multinucleated chemoresistant cancer cells found in heterogeneous solid tumors. Due in part to their apparent dormancy, the effect of PGCCs on cancer progression has remained largely unstudied. Recent studies have highlighted the critical role of PGCCs as aggressive and chemoresistant cancer cells, as well as their ability to undergo amitotic budding to escape dormancy. Our recent study demonstrated the unique biophysical properties of PGCCs, as well as their unusual migratory persistence. Here we unveil the critical function of vimentin intermediate filaments (VIFs) in maintaining the structural integrity of PGCCs and enhancing their migratory persistence. We performed in-depth single-cell analysis to examine the distribution of VIFs and their role in migratory persistence. We found that PGCCs rely heavily on their uniquely distributed and polarized VIF network to enhance their transition from a jammed to an unjammed state to allow for directional migration. Both the inhibition of VIFs with acrylamide and small interfering RNA knockdown of vimentin significantly decreased PGCC migration and resulted in a loss of PGCC volume. Because PGCCs rely on their VIF network to direct migration and to maintain their enlarged morphology, targeting vimentin or vimentin cross-linking proteins could provide a therapeutic approach to mitigate the impact of these chemoresistant cells in cancer progression and to improve patient outcomes with chemotherapy.

多倍体巨癌细胞（PGCC）是在异质​​实体瘤中发现的多核化学抗性癌细胞。部分由于它们的明显休眠，PGCC对癌症进展的影响仍未研究。最近的研究强调了PGCC作为侵袭性和化学耐药性癌细胞的关键作用，以及它们经历有丝分裂芽逃脱休眠的能力。我们最近的研究证明了PGCC的独特生物物理特性，以及它们异常的迁移持久性。在这里，我们揭示了波形蛋白中间丝（VIF）在维持PGCC的结构完整性和增强其迁移持久性方面的关键功能。我们进行了深入的单细胞分析，以检查VIF的分布及其在迁徙持久性中的作用。我们发现PGCC严重依赖于其独特分布和极化的VIF网络，以增强其从阻塞状态到未阻塞状态的过渡，以实现方向迁移。丙烯酰胺对VIF的抑制和波形蛋白的小干扰RNA敲低都显着降低了PGCC的迁移并导致PGCC体积的损失。由于PGCC依靠其VIF网络来指导迁移并维持其扩大的形态，因此靶向波形蛋白或波形蛋白交联蛋白可以提供一种缓解这些化学耐药性细胞对癌症进展的影响并通过化疗改善患者预后的治疗方法。丙烯酰胺对VIF的抑制和波形蛋白的小干扰RNA敲低都显着降低了PGCC的迁移并导致PGCC体积的损失。由于PGCC依靠其VIF网络来指导迁移并维持其扩大的形态，因此靶向波形蛋白或波形蛋白交联蛋白可以提供一种缓解这些化学耐药性细胞对癌症进展的影响并通过化疗改善患者预后的治疗方法。丙烯酰胺对VIF的抑制和波形蛋白的小干扰RNA敲低都显着降低了PGCC的迁移并导致PGCC体积的损失。由于PGCC依靠其VIF网络来指导迁移并维持其扩大的形态，因此靶向波形蛋白或波形蛋白交联蛋白可以提供一种缓解这些化学耐药性细胞对癌症进展的影响并通过化疗改善患者预后的治疗方法。