Molecular Mechanisms by Which S100A4 Regulates the Migration and Invasion of PGCCs With Their Daughter Cells in Human Colorectal Cancer

Frontiers in Oncology

Fei Fei¹  Zhen Wei¹  Chunyuan Li²  Shiwu Zhang²  Yuwei Li³  Yi Zhang³  Kai Liu⁴  Jiaxing Du⁵  Bo Li⁵ 

[1] Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China;Department of Pathology, Tianjin Union Medical Center, Tianjin, China;Departments of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China;Graduate School, Tianjin Medical University, Tianjin, China;Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, China;

关键词: polyploid giant cancer cells;    colorectal cancer;    metastasis;    S100A4;    TRIM21;   

DOI  :  10.3389/fonc.2020.00182

来源: DOAJ

【 摘 要 】

Recently, an increasing number of evidences have shown that polyploid giant cancer cells (PGCCs) could generate daughter cells with a strong migration and invasion ability, which have been implicated in cancer recurrence and metastasis. However, the underlying molecular mechanisms of PGCCs with their daughter cells remain largely unclear. In vitro and in vivo experiments combined with 222 cases of human colorectal cancer (CRC) samples were used to identify the molecular mechanisms of S100A4-related proteins regulating the invasion and metastasis of PGCCs with their daughter cells. PGCCs with their daughter cells had high migration, invasion, and proliferation abilities compared to control cells; these were significantly inhibited after S100A4 knockdown. The high expression of cathepsin B, cyclin B1, TRIM21, and Annexin A2 were significantly downregulated after S100A4 knockdown, while the overexpression of S100A4, cathepsin B, cyclin B1, and S100A10 were significantly downregulated after TRIM21 knockdown in PGCCs with their daughter cells. The tumorigenic and metastatic ability of PGCCs with their daughter cells in vivo was significantly stronger compared to the untreated cells, which was significantly decreased after S100A4 knockdown. Moreover, the expression of S100A4-related proteins was positively correlated with the malignancy degree of human CRC, and maintained a high level in lymph node metastasis. S100A4 and TRIM21 may regulate each other to affect the expression and subcellular localization of cyclin B1, and participate in regulating the structure and function of Annexin A2/S100A10 complex, affecting downstream cathepsin B, resulting in the invasion and metastasis of PGCCs with their daughter cells. Besides, 14-3-3 ζ/δ and Ezrin may be involved in the motility and invasion of PGCCs with their daughter cells via cytoskeletal constructions with S100A4.

【 授权许可】

Unknown