Fig. 5

A schematic illustration of key molecular signaling pathways in metastasis. A By overstimulating the phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways, the HGF/c-Met signaling pathway advances cancer cell metastasis and causes 15-PGDH downregulation. PRL3 transcripts are found in abundance in CRC liver metastases, and the PRL3-induced augmentation of EMT is contingent upon EGFR activation. Additionally, PRL3 enhances cell invasion and increases MMPS expression by activating AKT. In conjunction with these factors, L1CAM, TGF-β, MACC1, CXCR4, Trop-2, CAFs, and ZFP57 are also implicated in the progression of CRC liver metastasis. B Certain oncogenes are associated with lung metastasis in colorectal cancer (CRC). KRAS mutations often lead to lung metastasis, whereas its wild-type counterpart tends to result in liver metastasis. Genes REG1B, TGM6, NTF4, PNMA5, and HOXC13 have been identified as key candidates associated with colon cancer lung metastasis. C Certain molecular pathways are involved in colorectal cancer's peritoneal metastasis. A low mutation load in tumor suppressor gene FBXW7 is observed in this metastasis type, whereas a high mutation load of FBXW7 in primary tumors associates with less metastasis. Mucin glycoproteins, like CD44 and MUC1, play crucial roles in metastasis, with the latter promoting EMT and inhibiting cell apoptosis. Other proteins, including TIMP-2, IGF-1, and HIF-1α, increase in peritoneal metastasis, aiding tumor cell settlement in the subperitoneal region. An enrichment of CMS4 subtype is noted in primary tumors with peritoneal metastasis, while peritoneal metastasis presents comparable KRAS mutation rates to primary tumors but shows higher prevalence of GNAS and BRAF pathways. Transcriptome analysis reveals peritoneal metastasis has more mutations in the Wnt/β-catenin signaling pathway's negative regulators, TET2 mutations, mismatch repair gene mutations, and increased tumor mutational burden compared to primary tumors