Table 1.
YAZ/TAZ-mediated oncogenesis in BC.
| Cell types | Context | Partners | Transcriptional outputs | Functions | Main reference |
|---|---|---|---|---|---|
| Mammary epithelium | MCF10A | TEADs | YAP/TEAD target genes | YAP is required for mammary epithelial cell transformation, oncogenic growth and metastasis. | [10, 13, 15, 23, 25–27, 32] |
| MCF10A | TEADs | TAZ/TEAD target genes | TAZ is required for mammary epithelial cell transformation, oncogenic growth and metastasis, as well as BC stemness and chemoresistance. | [24, 28–32] | |
| MCF10A | TEADs | AREG | YAP-induced AREG expression is required for YAP-mediated cell proliferation and migration, but not EMT. | [33] | |
| MCF10A | TEADs and B-MYB | B-MYB and mitotic genes | YAP and B-MYB are critical for YAP-mediated entry into mitosis. | [34] | |
| Mouse mammary stem cells | / | / | YAP activation in mouse MaSCs causes rapid formation of large tumours in an orthotopic allograft mouse model. | [35] | |
| Mammary epithelial cell reprogramming | / | / | Transient upregulation of exogenous YAP/TAZ in primary mammary epithelial cells can efficiently reprogramme them into MaSC-like cells. | [36] | |
| PyMT-induced mammary tumourigenesis | / | / | YAP is required for the terminal differentiation of mammary epithelia, and PyMT-induced mammary tumour growth. | [37] | |
| Breast epithelial lineage commitment | SWI/SNF | Luminal and basal cell-specific genes | TAZ/SWI/SNF complex can repress the expression of luminal cell-specific genes and activate basal cell-specific genes. | [38] | |
| DMBA-induced mammary tumourigenesis | / | / | TAZ regulates mammary gland morphogenesis and carcinogen-induced mammary tumourigenesis. | [39] | |
| Apc loss-induced mammary tumourigenesis | TEADs and BRD4 | Growth-regulating genes | YAP/TAZ and BRD4-mediated transcription is responsible for the transcriptional addiction in BC. | [40] | |
| Mob1a/b knockout-induced mammary tumourigenesis | TEADs | KRT14, KRT5, EGFR, and KRT17 | TAZ is activated in human premalignant BLBC and a key driver of human BLBC. | [41] | |
| p53 loss-induced mammary tumourigenesis | / | / | YAP overexpression is required for p53 loss-induced tumourigenesis. | [42–44] | |
| t-ASPP2-associated ILC | / | / | YAP activation induced by truncation variant of ASPP2 contributes to tumour growth and progression. | [45] | |
| Luminal BC | GPER-mediated BC | TEADs | CTGF, CYR61, EDN1, and EGR1 | YAP/TAZ is required for GPER-induced gene transcription, BC cell proliferation and migration, and tumour growth. | [48] |
| Lats1/2 knockout mammary epithelium | TEADs | Luminal and basal cell-specific genes | YAP/TAZ cooperates with ERα and regulates the breast cell fate. | [49] | |
| ERα+ BC | TEADs, ER and MED1 | E2/ERα-target genes | YAP/TAZ is required for estrogen-induced transcription and BC growth. | [50] | |
| ERα+ BC | TEADs | ESR1 | YAP/TAZ is required for the transcriptional repression of ESR1. | [51] | |
| ERα+ BC | TEADs | VGLL3 | YAP/TAZ-induced expression of VGLL3 is required for NCOR2/SMRT complex-mediated transcriptional repression of ESR1 gene. | [52] | |
| ERα+ BC | TEADs | ESR1 | YAP inhibits ERα and ER+ BC growth by disrupting a TEAD-ERα signalling axis. | [53] | |
| Tamoxifen-resistant BC | TEADs | CTGF, CYR61, Glut3 and ERα | YAP, CTGF and CYR61-induced transcriptional repression of ERα confers resistance to tamoxifen in BC. | [54] | |
| CDK4/6 inhibitors-resistant ER+ BC | TEADs | CDK6 | Yap/TAZ-mediated CDK6 overexpression is required for FAT1 or RB1 loss-associated clinical resistance to CDK4/6 inhibitors in ER+ BC. | [58] | |
| HER2+ BC | ILK-driven HER2+ BC | TEADs | YAP/TAZ target genes | YAP/TAZ activity is required for ERBB2 and ILK-driven mammary tumourigenesis. | [60–62] |
| EphA2-driven HER2+ BC | TEADs | SLC1A5 and GLS | YAP/TAZ-mediated transcriptions are required for EphA2-induced glutamine metabolism in HER2+ BC. | [63–65] | |
| Mechanical signalling-mediated oncogenic activation | / | / | YAP/TAZ activation accounts for the transcriptional responses downstream of oncogenic signalling. | [66] | |
| Lapatinib-resistant HER2+ BC | TEADs | AREG | YAP/TAZ-dependent transcriptions are required for rigid microenvironments-modulated lapatinib-resistance in HER2+ BC. | [70] | |
| Anti-HER2 treatment-resistant BC | TEADs | Survivin and mTORC1 | YAP/TAZ-mediated transcriptions are required for mevalonate pathway-mediated resistance to HER2-targeted treatments. | [71] | |
| Trastuzumab-resistant BC | / | / | Over-expression of YAP/TAZ as well as HER-3 and HER2/HER3 heterodimer is synchronously remarkable in trastuzumab-resistant BC cells. | [72] | |
| TNBC | RASSF1A inactivation-associated TNBC | TBX3, β-catenin and TEADs | BIRC5, BCL2L and MYC | β-catenin/TBX3-YAP/TEAD complex-mediated transcriptions are required for RASSF1A-loss or RASSF1C-activated BC invasive phenotypes. | [76] |
| TNBC with chromosome 5q loss | TEADs | YAP/TAZ target genes | YAP/TAZ activity is required for KIBRA loss-derived metastatic and CSC-like behaviours. | [77] | |
| TNBC with SYNPO2 downregulation | TEADs | CYR61 and CTGF | Inhibition of YAP/TAZ activity is required for Synaptopodin-2 function in metastasis suppression of TNBC. | [78] | |
| AP1/YAP-expressed BC | AP1 and TEADs | AP1-YAP-TEADs target genes | YAP/TAZ/TEAD and AP-1 association at enhancers drives oncogenic growth of BC. | [79] | |
| ZEB1/YAP-expressed BC | TEADs and ZEB1 | ZEB1-YAP-TEADs target genes | ZEB1 and YAP/TEAD interaction stimulates the BC cell aggressiveness. | [80] | |
| KLF5 overexpression-associated TNBC | TEADs and KLF5 | KLF5-YAP-TEADs target genes | KLF5 and YAP/TEAD interaction stimulates the BC cell proliferation and migration. | [81, 82] | |
| Taxol-resistant TNBC cells | TEADs | CYR61 and CTGF | YAP/TAZ and their downstream transcriptional targets Cyr61 and CTGF are required for Taxol-resistance in BC cells. | [83–85] | |
| VEGF/NRP2 signalling-activated TNBC | TEADs | Rad51 | YAP/TAZ-dependent Rad51 expression contributes to the resistance of TNBC cells to cisplatin. | [86, 87] | |
| Recurrent and mesenchymal BC cells | TEADs | CYR61, CTGF and ferroptosis-associated genes | YAP/TAZ activity is required for DDR2-induced ferroptosis susceptibility of recurrent and mesenchymal BC cells. | [88] | |
| BCSCs | Loss of Scribble or activation of EMT | TEADs | CTGF and Survivin | YAP/TAZ are required to sustain self-renewal and tumour-initiation capacities in BCSCs. | [24] |
| Activation of serum response factor | TEADs and SRF | IL6, THBS1, ETS1, DLL1 etc. | SRF-YAP association-induced IL6 expression is critical for YAP-induced stemness in mammary epithelial cells and BC. | [93] | |
| / | TEADs | YAP/TAZ target genes | TAZ is required for metastatic activity and chemoresistance of BCSCs. | [95] | |
| ROR1-induced chemotherapy-resistance of BCSCs | TEADs | YAP/TAZ target genes | YAP activity is required for ROR1-mediated BCSC maintenance, self-renewal, and drug resistance. | [96–98] | |
| TMEs | ECMs and CAFs | TEADs | LM511 | TAZ regulates the transcription of LM511 and the formation of a LM511 matrix, and then the LM511/α6Bβ1 association can contribute the self-renewal and tumour-initiation of BCSCs. | [103] |
| TEADs | Cytoskeletal regulator genes, including ANLN, DIAPH3 and MYL9 | SRC-mediated YAP activation is required for CAFs to promote matrix stiffening, cancer cell invasion and angiogenesis in BC. | [104] | ||
| TEADs | IL11 and IL15 | YAP-mediated breast stromal CAF activation can promote angiogenesis in a VEGF-independent manner. | [105, 106] | ||
| TEADs | CYR61, CTGF, BIRC5, ANLN, MYL9 etc. | YAP/TAZ activation in CAFs is responsible for CCM3 loss-induced BC metastasis. | [107] | ||
| TEADs or β-catenin | ECM remodelling-associated genes | YAP/TAZ signalling is required for DKK3-mediated tumour-promoting activities of CAFs in BC. | [108] | ||
| TEADs | CTGF, GLS1 and SLC1A3 | Mechanics-mediated YAP/TAZ activity is required for coordinating the metabolic crosstalk between CAFs and BC cells. | [109, 110] | ||
| Adipocytes | TEADs | Resistin | TAZ-Resistin signalling promotes the BC growth and stemness. | [112] | |
| TIME | TEADs and p65 | HK2 | Activated YAP cooperates with TEAD-p65 to promote BC cell migration and metastasis. | [115] | |
| TEADs | YAP/TAZ target genes | YAP activity is required for Cdh1 and Pik3ca mutations-induced immune-related ILC of the breast. | [118] | ||
| TEADs | PD-L1 | YAP/TAZ promote BC immune evasion through the transcriptional regulation of PD-L1. | [123] | ||
| TEADs | PD-L1 and IL34 | TAZ-mediated transcriptions induce the proliferation and migration of TAMs and inhibited T cell infiltration, thereby forming an immunosuppressive microenvironment in TNBC. | [124] |
A systematic review of YAP/TAZ-mediated oncogenic roles in various BC subtypes, BCSCs and TMEs.