Evolutionary adaptation and asymmetric inheritance of polyploid giant cancer cells in esophageal squamous cell carcinoma.

Abstract

Polyploid Giant Cancer Cells (PGCCs) play a critical role in tumor progression due to their distinctive biological behaviors. However, the mechanisms by which PGCCs regulate their composition and structure to adapt to dynamic environments during their formation remain poorly understood. In this study, we used multicolour labeling of major organelles in esophageal squamous cell carcinoma (ESCC) cells combined with high- and super-resolution time-lapse imaging to monitor induced PGCCs in three dimensions. In addition to abnormal PGCC division, we observed nuclear dynamics and transient cell-in-cell formations. PGCCs exhibited cell cycle abnormalities, including prolonged G1/S transitions, asynchronous micronuclei, and intranuclear mitosis. Notably, early progeny continued dividing despite cell cycle dysregulation, resulting in asymmetric offspring. Quantitative analysis of subcellular structures revealed asymmetric inheritance of organelles, particularly mitochondria and the Golgi apparatus, in recurrent cells. These adaptive mechanisms in PGCCs may also be relevant in the context of anticancer treatments, contributing to the heterogeneity of recurrent tumours arising from early PGCC progeny populations.