Table 2 Summary of the tumor-suppressive roles of YAP/TAZ in different tumor types and cellular contexts
From: New insights into the ambivalent role of YAP/TAZ in human cancers
Mechanisms | Cancer types | Partners | Transcriptional outputs | Functions | Main reference |
|---|---|---|---|---|---|
Interfere with the transcription of key oncogenes | ER + breast cancer | ERa | / | YAP-ER association competes with ERα for binding to TEAD and inhibits ERα-associated transcription and function | [109] |
AR + prostate cancer | AR | / | YAP-AR association competes with AR for binding to TEAD and inhibits AR-associated transcription and function | [110] | |
ccRCC | TEAD-Hif-2α | GLUT1 and VEGF | YAP-TEAD interaction competes with TEAD-Hif-2α complex to decrease HIF-2α target gene expression and reduce tumour growth | [111] | |
Hematological malignancies | / | MYC | TAZ elicits an antitumorigenic and proapoptotic function by repressing MYC expression and its oncogenic function | [112] | |
Facilitate the transcription of oncosuppressor genes | Mammalian cells | / | LATS1/2, AMOT and NF2 | YAP/TAZ activation induces the expressions of their negative regulators to establish a negative feedback loop between YAP/TAZ and their inhibitors | |
Live cancer | / | NR4A1 | YAP promotes the pro-apoptotic and anti-tumour effects medicated by NR4A1, which in turn functions as a feedback inhibitor of YAP to promote its degradation | [115] | |
ER + breast cancer | VGLL3-TEADs and NCOR2/SMRT | VGLL3 | VGLL3-TEAD complex can recruit the NCOR2/SMRT repressor to the super-enhancer of ESR1 gene to reduce its transcription | [119] | |
Breast cancer | / | Immunosurveillance-related genes | YAP induces the expression of immunosurveillance-related genes | [120] | |
Lung squamous cell carcinoma | / | GPX2 | YAP activation leads to excessive accumulation of reactive oxygen species by downregulating the antioxidant enzyme GPX2 | [121] | |
Mouse MC38 colon cancer cells | / | Wisp2 and Ccdc80 | YAP activation causes a growth inhibitory effect on tumor cells | [122] | |
MCPyV-positive Merker cell carcinoma | TEADs | MCPyV LT | YAP/TAZ suppress tumor growth through TEAD-dependent transcriptional repression of MCPyV LT | [123] | |
Enhance the susceptibility to apoptosis-inducing agents | Multiple cancer cell lines | p73 and PML | p73-associated target genes | YAP/TAZ cooperate with p73 to induce p73-associated target genes and accelerate tumor cell apoptosis | |
Prostate carcinoma | EGR-1 | Bax | YAP/TAZ enhance the susceptibility to radiation-induced apoptosis | [129] | |
Hematologic malignancies | / | Apoptosis-related genes | YAP activation can trigger DNA damage-induced apoptosis | [130] | |
Pancreatic cancer | TEADs | CDA, CTGF and AMOTL2 | YAP enhances gemcitabine intracellular availability in tumors by down-regulating multidrug transporters | [131] | |
Promote the ferroptosis | RCC | / | EMP1 and NOX4 | TAZ activation can enhance the susceptibility of RCC to ferroptosis | [134] |
Ovarian cancer | / | ANGPTL4 and NOX2 | TAZ-ANGPTL4-NOX2 signaling axis mediates the cell density-regulated ferroptosis | [135] | |
Mesothelioma cells | / | ACSL4 and TFRC | YAP activation enhances cellular sensitivity to ferroptosis | [136] | |
Shape the suppressive tumor microenvironment | Liver cancer | / | CYR61, CTGF and Ankrd1 | Activated YAP in the peritumoral hepatocytes represses the primary liver tumor growth and melanoma-derived liver metastases | [138] |
Gastric cancer | / | CD54 | YAP/TAZ-CD54 signaling axis activation in CXCR2-CD44-tumor-specific neutrophils can suppress gastric cancer growth | [139] | |
Multiple cancer cell lines | / | / | YAP/TAZ-activated tumor cells can secrete nucleic-acid-rich extracellular vesicles to induce anti-tumor immunity | [140] | |
Counteract the key oncogenic pathway | Colorectal cancer | / | KLF6 | YAP activation counteracts the Wnt signaling to repress colorectal cancer growth |