Research progress and prospects on the mechanisms of circulating tumor cells in the invasion and metastasis of cholangiocarcinoma

doi:10.19401/j.cnki.1007-3639.2025.10.008

Abstract

Abstract:

Cholangiocarcinoma, as a malignant tumor with strong invasiveness and poor prognosis, has a complex metastasis mechanism, and urgently needs in-depth research. Circulating tumor cells (CTC), as the key cell type for tumor cells to shed from the primary site and enter the bloodstream, have significant research significance. In recent years, studies have found that the invasive pseudopodia of CTC play a significant role in the migration and invasion of tumor cells. Among them, in terms of signal transduction pathways, the Rho family GTPases (RhoA, Rac1, Cdc42) work in coordination to regulate the contractility of the pseudofoot, the branching polymerization and orientation of actin, and the phosphoinositide3-kinase/protein kinase B (PI3K/AKT) pathway promotes the assembly of actin and cross-communicates with the Rho family by activating AKT. At the molecular mechanism level, long non-coding RNAs regulate the expression of pseudopolypod-related genes by adsorbing miRNAs and other means. Matrix metalloproteinase (MMP) degrades the extracellular matrix (ECM) to form an invasion positive feedback. In terms of the microenvironment, cancer-associated fibroblast (CAF) and the cytokines such as transforming growth factor-β (TGF-β) secreted by macrophages, epidermal growth factor (EGF), and interleukin-6 (IL-6) activate pseudopodia to form signal transduction pathways. ECM hardness and fiber arrangement affect the extension direction of pseudopodia through mechanical force conduction. This article conducted a comprehensive analysis of the biological characteristics of CTC, the formation mechanism of invasive pseudopodia in cholangiocarcinoma, the metastatic features of cholangiocarcinoma cells and their clinical significance, as well as the role of CTC in the metastatic process of cholangiocarcinoma, in order to summarize the existing research results, explore potential therapeutic targets and future research directions, and provide new ideas for the clinical treatment of cholangiocarcinoma.

Key words: Circulating tumor cells, Cholangiocarcinoma, Invasive pseudopodia, Metastasis, Tumor microenvironment

CLC Number:

R735.8

YU Xue, SHEN Tianhao, ZHOU Cheng, LIU Yu, JIANG Tinghui, LI Wei, ZHU Yongqiang, LIU Yan. Research progress and prospects on the mechanisms of circulating tumor cells in the invasion and metastasis of cholangiocarcinoma[J]. China Oncology, 2025, 35(10): 952-958.

Figures/Tables 2

References 51

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Research direction	Classification	Mechanism and function	Reference
Signal pathway	Rho family GTP enzymes	RhoA, Rac1 and Cdc42 work in coordination and division of labor, respectively regulating the contractility of pseudopodia, the branching polymerization of actin and the guidance of filamentous pseudopodia, forming a precise regulatory network	[15]
	The PI3K/AKT pathway	By generating PIP3 to activate AKT, it directly promotes actin assembly and cross-communicates with the Rho family, synergistically driving the formation of pseudopodia	[26-27]
Microenvironment interaction	Physical factors	The hardness of ECM and the arrangement of fibers affect the extension direction of pseudopodia, and regulate the migration behavior through mechanical force conduction	[31-32]
	Cytokine	CAFs secrete TGF-β and EGF, and macrophages polarize to produce IL-6, etc., activating pseudopodia to form signaling pathways	[33-34]
Molecular mechanism	Key protein	Cortactin stabilizes the actin network and enhances the structural stability of pseudopodia. MMPs degrade the extracellular ECM, forming an invasive positive feedback	[42]
	LncRNA	Indirectly promote the synthesis of pseudopod-related proteins by adsorbing miRNAs or regulating gene expression	[43]