Fig. 5

Details of CBX members regulate TGF-β, Notch, HFI-1, P53/P21, E2F1/BIRC5, Rho GTPase, PRDM1/c-FOS signalling pathways in tumours and mechanism. (A) CBX3 could exert the transcriptional inhibition of HP1 family proteins, downregulating the expression of downstream target genes, promoting the activation of TGF-β signalling pathway in PC cells, and play the role of carcinogenic factor. CBX7 could play a role as a cancer suppressor in CCA cells by regulating the activation of TGF-β/PI3K/AKT signalling pathway, but the important role of CBX7 transcriptional regulation mechanism is still unclear. CBX4 could inhibit the expression of downstream target genes through classical PRC1-dependent pathway transcription, promote the activation of Notch signalling pathway in BC cells, and play a role as a carcinogenic factor. However, CBX8 inhibits the expression of downstream target genes through non-classical PRC1-independent pathway transcription, promotes the activation of Notch signalling pathway in BC cells, and plays a role as a carcinogenic factor. (B) CBX4, independent of the classical PRC1-dependent pathway, exerts SUMO E3 ligase activity to enhance the transcriptional activity of downstream target genes, overactivates HIF-1α signalling pathway in HCC cells, and acts as a carcinogenic factor. However, whether CBX4 promotes the activation of HIF-1α signalling pathway in OS cells through the same pathway remains to be further explored. CBX3 could play a role as a carcinogenic factor by exerting transcriptional inhibition mediated by HP1 family proteins, silencing the expression of downstream target genes, inhibiting the activation of P53/P21 signalling pathway in TSCC and CRC. However, the transcriptional regulatory mechanisms of CBX3 and CBX8 in regulating P53/P21 signalling pathway activation in ESCC, UBC, and HCC remain unclear. CBX7 could interact with HDAC2 independently of the classical PRC1-dependent pathway in thyroid cancer, lung cancer and brain glioma cells, regulate histone acetylation in the promoter region of downstream target genes, transcriptively activate or silence the expression of downstream target genes, and reduce migration, invasion and activation of cell cycle-related signalling pathways, acting as a cancer suppressor. The low expression of CBX5 in EGFR-mutated LUAD cells could inhibit the expression of E2F1, weaken the transcriptional activation of E2F1, downregulate the expression of anti-apoptotic gene BIRC5, inhibit the activation of anti-apoptotic signalling pathway of E2F1/BIRC5, induce apoptosis, and enhance the sensitivity of patients to EGFRi treatment. Exert tumour-suppressive effect. At the same time, the combination of epigenetic regulatory factor-related small-molecule inhibitors BETi and EGFRi could restore the expression of CBX5 and re-improve the sensitivity of LUAD resistant patients with EGFR mutation to EGFRi treatment. (C) CBX3 could downregulate the expression of downstream target genes through the transcriptional inhibition mediated by HP1, promote the activation of Rho GTPase signalling pathway in LUAD cells, and play a role in tumour promotion. CBX8 could also transcriptionally inhibit the transcriptional activity of downstream target genes, promote the activation of Rho GTPase signalling pathway in GBM, BC and lung cancer, and play a tumour-promoting role. However, more evidence is needed to confirm whether CBX8 exerts transcriptional inhibition through the classical PRC1-dependent pathway. CBX8 could act as a methylation reader in UBC, identify H3K27me3 catalysed by PRC2 in the downstream target gene PRDM1 promoter region, recruit non-classical PRC1-BCOR complex to bind to PRDM1 promoter and promote H2AK119ub1. Then, the expression of PRDM1 is inhibited by non-classical PRCI-independent transcriptional pathway, so as to upregulate the expression of c-FOS, promote the activation of PRDM1/c-FOS signalling pathway, induce EMT, and promote the malignant proliferation and metastasis of UBC cells.