J Cancer 2022; 13(9):2954-2969. doi:10.7150/jca.74211 This issue Cite

Research Paper

PLK4 is a key molecule in the formation of PGCCs and promotes invasion and migration of progeny cells derived from PGCCs

Fangmei Fu1#, Lankai Chen2#, Xiaohui Yang2, Linlin Fan3, Mingqing Zhang2, Shuo Chen4, Minying Zheng1, Ming Gao5✉, Shiwu Zhang1✉

1. Department of Pathology, Tianjin Union Medical Center, Nankai University, Tianjin, 300121, P.R. China.
2. Nankai University School of Medicine, Nankai University, Tianjin, 300071, P.R. China.
3. Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, P.R. China.
4. Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, P.R. China.
5. Department of Thyroid Surgery, Tianjin Union Medical Center, Tianjin, P.R. China.
# These authors equally contributed to the paper.

Citation:
Fu F, Chen L, Yang X, Fan L, Zhang M, Chen S, Zheng M, Gao M, Zhang S. PLK4 is a key molecule in the formation of PGCCs and promotes invasion and migration of progeny cells derived from PGCCs. J Cancer 2022; 13(9):2954-2969. doi:10.7150/jca.74211. https://www.jcancer.org/v13p2954.htm
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Abstract

Graphic abstract

Purpose: Cancer stem cells (CSCs) are the evil source of tumor metastasis and recurrence. Polyploid giant cancer cells (PGCCs) that exhibit the characteristics of CSCs produced daughter cells via asymmetric division. The molecular mechanisms of daughter cells derived from PGCCs with high migration, invasion, and proliferation abilities in colorectal cancer (CRC) are explored in this paper based on the bioinformatics analysis.

Materials and Methods: We characterized the expression of CSC-related genes in CRCs by analyzing the mRNAsi of The Cancer Genome Atlas and survival time. Weighted gene co-expression network analysis was performed to identify the modules of the hub and key genes. The migration, invasion, and proliferation abilities of cells, the expression of epithelial-mesenchymal transition (EMT)-related proteins and polo-like kinase 4 (PLK4) were compared in LoVo and Hct116 cells with and without bufalin treatment. In addition, the expression and subcellular location of cell division cycle 25C (CDC25C) in cells before and after PLK4 knockdown were assessed.

Results: Eight hub genes were screened out and positively association with mRNAsi in CRCs based on bioinformatic analysis. Among them, checkpoint Kinase-1 (CHEK1), budding uninhibited by benzimidazoles 1 Homolog Beta (BUB1B) and PLK4 were closely associated with the prognosis of CRC patients. Bufalin could induce the formation of PGCCs in LoVo and Hct116 cell lines. PLK4 was overexpressed in PGCCs with progeny cells and progeny cells derived from PGCCs had strong migration and invasion abilities by expressing epithelial-mesenchymal transition (EMT)-related proteins. PLK4 could interact with CDC25C and promote CDC25C phosphorylation which was associated with the formation of PGCCs. Decreasing CDC25C expression in both LoVo and Hct116 PGCCs with progeny cells, while levels of pCDC25C-ser216 and pCDC25C-ser198 were increased in LoVo and decreased in Hct116 PGCCs with progeny cells. pCDC25C-ser216 located in the cytoplasm and pCDC25C-ser198 located in the nucleus in cells after bufalin treatment. Furthermore, expression of CDC25C, pCDC25C-ser216, and pCDC25C-ser198 was downregulated after PLK4 knockdown. Furthermore, the expression level of PLK4 was associated with differentiated degree, and lymph node metastasis in human CRC tissues.

Conclusion: PLK4 contributes to the formation of PGCCs by regulating the expression of CDC25C and is associated with the expression and subcellular location of CDC25C, pCDC25C-ser216 and pCDC25C-ser198.

Keywords: PLK4, CDC25C, bufalin, colorectal cancer, polyploid giant cancer cells, epithelial-mesenchymal transition


Citation styles

APA
Fu, F., Chen, L., Yang, X., Fan, L., Zhang, M., Chen, S., Zheng, M., Gao, M., Zhang, S. (2022). PLK4 is a key molecule in the formation of PGCCs and promotes invasion and migration of progeny cells derived from PGCCs. Journal of Cancer, 13(9), 2954-2969. https://doi.org/10.7150/jca.74211.

ACS
Fu, F.; Chen, L.; Yang, X.; Fan, L.; Zhang, M.; Chen, S.; Zheng, M.; Gao, M.; Zhang, S. PLK4 is a key molecule in the formation of PGCCs and promotes invasion and migration of progeny cells derived from PGCCs. J. Cancer 2022, 13 (9), 2954-2969. DOI: 10.7150/jca.74211.

NLM
Fu F, Chen L, Yang X, Fan L, Zhang M, Chen S, Zheng M, Gao M, Zhang S. PLK4 is a key molecule in the formation of PGCCs and promotes invasion and migration of progeny cells derived from PGCCs. J Cancer 2022; 13(9):2954-2969. doi:10.7150/jca.74211. https://www.jcancer.org/v13p2954.htm

CSE
Fu F, Chen L, Yang X, Fan L, Zhang M, Chen S, Zheng M, Gao M, Zhang S. 2022. PLK4 is a key molecule in the formation of PGCCs and promotes invasion and migration of progeny cells derived from PGCCs. J Cancer. 13(9):2954-2969.

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