New insights into the ambivalent role of YAP/TAZ in human cancers

Luo, Juan; Deng, Liang; Zou, Hailin; Guo, Yibo; Tong, Tongyu; Huang, Mingli; Ling, Gengqiang; Li, Peng

doi:10.1186/s13046-023-02704-2

Journal of Experimental & Clinical Cancer Research

Table 1 Summary of the oncogenic roles of YAP/TAZ in different tumor types and cellular contexts

From: New insights into the ambivalent role of YAP/TAZ in human cancers

Functions	Cancer types	Partners	Transcriptional outputs	Mechanisms	Main reference
Cell proliferation and anti-apoptosis	Multiple cancer cells	TEADs	CTGF and BIRC5	YAP/TAZ-mediated transcription regulates cell growth and anti-apoptosis	[9,10,11, 34,35,36]
	Multiple cancer cells	TEAD and AP-1 family members	S-phase entry and mitosis-related genes	YAP/TAZ cooperates with TEAD and AP-1 family transcription partners on enhancers to induce the transcription of YAP-specific proliferation genes	[38,39,40,41]
	Liver cancer	TEADs and TET1	TET1	YAP-induced the expression of TET1 can cooperate with TEADs to facilitate the transcription of YAP/TAZ target genes	[45]
	Multiple cancer cells	TEADs and NuRD	DDIT4 and Trail	YAP/TAZ-TEAD complex recruits the NuRD complex to repress the expression of DDIT4 and Trail, thereby promoting mTORC1 activation and cell survival	[46]
	Multiple cancer cells	YY1 and EZH2	p27 or TGFBR2	YAP/TAZ recruit EZH2 on the genome to repress the expression of p27 or TGFBR2, thereby overcoming cell-cell contact inhibition and promoting cell hyperproliferation in human cancer cells	[47, 48]
Migration and invasion	Breast cancer	TEADs, ZEB1 and AP-1 family members	Cancer aggressiveness-associated genes	YAP/TAZ-TEAD complex cooperates with ZEB1 and AP-1 family members to directly activate the transcriptions of cancer aggressiveness-associated genes	[52,53,54]
	Prostate cancer	PRDM4	ITGB2	YAP/PRDM4-mediated ITGB2 expression can promote cell migration	[55]
	Gastric cancer	TEADs and FOS	ARHGAP29	YAP promotes the expression of ARHGAP29 to suppress the RhoA-LIMK-cofilin pathway, thereby promoting cell migration	[56]
Drug resistance	Breast cancer	TEADs	CTGF and CYR61	TAZ-mediated expression of CYR61 and CTGF promotes the resistance to taxol and doxorubicin in breast cancer	[57, 58]
	Colorectal cancer	TEADs	COX-2	YAP-induced COX-2 expression is associated with the increased taxol resistance in colorectal cancer	[59]
	Esophageal carcinoma	TEADs	EGFR	YAP-induced EGFR expression is associated with the increased resistance to 5-FU and docetaxel in esophageal carcinoma	[60]
	BRAF-mutated cancer cells	TEADs	BCL2L1	YAP-mediated BCL2L1 expression contributes to the BRAF inhibitor resistance in different BRAF-mutated cancer cells	[64]
	ER + metastatic breast cancer	TEADs	CDK6	YAP-induced CDK6 expression is responsible for the CDK4/6 inhibitor resistance in metastatic breast cancer	[65]
	Lung adenocarcinoma	TEADs and EP300	MYC and CD155	YAP mediated-phase separation and transcription contribute to the interferon-γ-dependent immunotherapy adaptive resistance	[66]
Stemness regulation	Breast cancer	TEADs and SRF	IL6	SRF-IL6 axis is the critical mediator of YAP-induced stemness in mammary epithelial cells and breast cancer	[69]
	Esophageal cancer	TEADs	SOX9	YAP regulates the transcription of SOX9 and endows esophageal cancer cells with stem-like properties	[70]
	Pancreatic ductal adenocarcinoma	PAF1 and TEADs	SOX9	PAF1 cooperates with YAP/TEAD to induce the transcription of SOX9, and which endows pancreatic cancer cells with stem-like properties	[71]
	Lung cancer	E2F1 and OCT4	SOX2	YAP binding to E2F1 and/or OCT4 upregulates SOX2 expression, thereby enhancing self-renewal of CSCs	[72]
Metabolic reprogramming	Glioblastoma	TEADs	GLUT3	YAP-mediated glucose uptake through upregulating GLUT3 promotes tumor cell growth	[74]
	Multiple cancer cells	TEADs	Glycolysis-associated genes	YAP/TAZ-mediated transcriptions promote glycolysis and repress mitochondrial respiration, oxidative phosphorylation, as well as oxidative stress-induced cell death	[75]
	Hepatocellular carcinoma	HIF-1α	PKM2	Hypoxia-induced YAP/HIF-1α interaction promotes PKM2 gene expression and accelerates glycolysis	[76]
	Multiple cancer cells	TEADs	GLS1, SLC1A5, GOT1 and PSAT1	YAP/TAZ-mediated glutaminolysis promotes tumorigenesis in multiple cancer cells	[78, 79]
	Multiple cancer cells	TEADs	ODC1	YAP/TAZ-mediated ODC1 transcription promotes polyamine biosynthesis and the polyamine-eIF5A hypusination-LSD1 axis to drive tumorigenesis	[80]
Tumor angiogenesis	Multiple cancer cells	HIF1α	VEGF	YAP/TAZ can complex with HIF1α to promote VEGF expression and tumor angiogenesis and growth	[84, 85]
	Tumor-associated endothelial cells	STAT3	VEGF and TNFα	YAP/TAZ associate with STAT3 in tumor-associated endothelia cells to enhance TEAD-associated transcription and angiogenesis	[86,87,88]
	Tumor-associated endothelial cells	TEADs	SLC7A5	YAP/TAZ-mediated SLC7A5 transcription stimulates the import of amino acids and other essential nutrients to promote angiogenic growth	[89]
Tumor microenvironment regulation	Breast cancer	TEADs	LM511	TAZ regulates the matrix formation through transcriptionally regulating LMa5 expression, and which in turn contributes to the CSC-properties by activating TAZ	[92]
	Breast cancer	TEADs	ANLN and DIAPH3, MYL9	YAP regulates the expression of several cytoskeletal regulators and contributes to the matrix stiffening of breast cancer	[93]
	Multiple cancer cells	TEADs	PD-L1	YAP/TAZ-induced PD-L1 expression facilitates the establishment of an immunosuppressive TME in human cancers	[95]
	Colon cancer	/	IL4/6	YAP promotes tumorigenesis of colon cancer through increasing the expression of M2-promoting IL-4 and tumor-promoting IL-6 cytokines	[98]
	Prostate cancer	TEADs	CXCL5	YAP-induced CXCL5 upregulation in prostate cancer can attract CXCR2-expressing myeloid-derived suppressor cells, thereby blocking immune cell response and promoting tumor progression	[99]

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ISSN: 1756-9966

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