Molecular mechanism of vimentin nuclear localization associated with the migration and invasion of daughter cells derived from polyploid giant cancer cells

Sep 24, 2026

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Polyploid giant cancer cells (PGCCs), a cancer stem cell type induced by hypoxia, chemicals, radiotherapy, and Chinese herbal medicine, generate daughter cells that undergo epithelial–mesenchymal transition, driving recurrence and disseminated metastasis. Vimentin, a mesenchymal marker highly expressed in PGCCs and their daughter cells, supports migratory persistence. This study investigates how vimentin synergistically regulates PGCC-derived daughter cells to enhance invasive and metastatic properties, focusing on molecular drivers of vimentin nuclear localization and downstream transcriptional control.

LanguageEnglish

CategoryHealthcare

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Pages18

Reading Time45 min

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Fan et al. Journal of Translational Medicine (2023) 21:719 [https://doi.org/10.1186/s12967-023-04585-7](https://doi.org/10.1186/s12967-023-04585-7) Journal of Translational Medicine RESEARCH Open Access Molecular mechanism of vimentin nuclear localization associated with the migration and invasion of daughter cells derived from polyploid giant cancer cells Linlin Fan1†, Minying Zheng1†, Xinyue Zhou2†, Yongjun Yu3, Yidi Ning4, Wenzheng Fu3, Jing Xu5 and Shiwu Zhang1* Abstract Background Polyploid giant cancer cells (PGCCs), a specific type of cancer stem cells (CSCs), can be induced by hypoxic microenvironments, chemical reagents, radiotherapy, and Chinese herbal medicine. Moreover, PGCCs can produce daughter cells that undergo epithelial–mesenchymal transition, which leads to cancer recurrence and disseminated metastasis. Vimentin, a mesenchymal cell marker, is highly expressed in PGCCs and their daughter cells (PDCs) and drives migratory persistence. This study explored the molecular mechanisms by which vimentin synergistically regulates PGCCs to generate daughter cells with enhanced invasive and metastatic properties. Methods Arsenic trioxide (ATO) was used to induce the formation of PGCCs in Hct116 and LoVo cells. Immunocytochemical and immunohistochemical assays were performed to determine the subcellular localization of vimentin. Cell function assays were performed to compare the invasive metastatic abilities of the PDCs and control cells. The molecular mechanisms underlying vimentin expression and nuclear translocation were investigated by real-time polymerase chain reaction, western blotting, cell function assays, cell transfection, co-immunoprecipitation, and chromatin immunoprecipitation, followed by sequencing. Finally, animal xenograft experiments and clinical colorectal cancer samples were used to study vimentin expression in tumor tissues. Results Daughter cells derived from PGCCs showed strong proliferative, migratory, and invasive abilities, in which vimentin was highly expressed and located in both the cytoplasm and nucleus. Vimentin undergoes small ubiquitin-like modification (SUMOylation) by interacting with SUMO1 and SUMO2/3, which are associated with nuclear translocation. P62 regulates nuclear translocation of vimentin by controlling SUMO1 and SUMO2/3 expression. In the nucleus, vimentin acts as a transcription factor that regulates CDC42, cathepsin B, and cathepsin D to promote PDC invasion and migration. Furthermore, animal experiments and human colorectal cancer specimens have confirmed the nuclear translocation of vimentin. †Linlin Fan, Minying Zheng and Xinyue Zhou contributed equally to the paper. *Correspondence: Shiwu Zhang [zhangshiwu666@aliyun.com](zhangshiwu666@aliyun.com) Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[. The Creative Commons Public Domain Dedication waiver (](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[http://cre

FAQs

What is the study’s main focus regarding vimentin in cancer cells?

The study examines the molecular mechanism of vimentin nuclear localization and how it supports the migration and invasion of daughter cells derived from polyploid giant cancer cells.

How are polyploid giant cancer cells (PGCCs) generated in this research?

Arsenic trioxide (ATO) is used to induce PGCC formation in Hct116 and LoVo cells.

What molecular pathway links P62 to vimentin nuclear translocation?

P62 regulates vimentin nuclear translocation by controlling the expression of SUMO1 and SUMO2/3, enabling vimentin SUMOylation associated with nuclear localization.

Sep 24, 2026

Uploaded by Mimi