Fig. 1

The crosstalk between circRNAs and TME in cancer invasion and intravasation. In invasion and migration, circASAP1 and circRIP2 from tumor cells contribute to tumor-associated macrophage (TAM) recruitment through CSF-1 and CCL2, respectively, while CXCL8 from TAMs can affect circ_0026344 expression in tumor tissue when interacting with CCL20 to influence cell-cell adhesions. Many circRNAs target MMPs and TIMPs to degrade the basement membrane and interstitial matrix. Circ_005625, circFNDC3B, and other circRNAs can modulate integrins, CD44, collagen-1, and FN1 to influence the interaction between tumor cells and ECM. CircRNAs can contribute to cancer-associated fibroblast (CAF)-mediated remodeling of the ECM by targeting the YAP transcription factor. During intravasation, circRNAs regulate CXCR4 on TAMs, which are attracted by CXCL12 from perivascular fibroblasts to migrate toward the blood vessel. CircRNAs from cancer tissues can regulate the immune escape by targeting PD-L1 and influence angiogenesis by modulating VEGFA, VEGFR, SP1, and ISM1 expression. CircRNAs are involved in cancer cell survival in the circulation by targeting CD44 and anoikis-related protein Bcl-xL to resist cell arrest and anoikis