Table 1.

Published studies on YAP/TAZ-dependent anti-cancer therapy resistance

Type	Evidence	Proposed mechanism	References
Cytotoxic chemotherapy	Overexpression of TAZ in breast cancer cells promotes taxol and doxorubicin resistance	TAZ induces stem cell-related traits	[35, 92]
	Overexpression of TAZ in breast cancer cells promotes taxol resistance	TAZ activation induces CYR61/CTGF expression, and CYR61/CTGF knockdown blocks taxol-resistance	[101]
	YAP mediates resistance to various anti-tubulin drugs in HeLa and other cancer cell lines	Anti-tubulin drug treatment activates Cdk1 to phosphorylate and inactivate YAP	[102]
	5-FU treated colon cancer liver metastasis shows increased YAP expression, and YAP expression levels predict patient survival	c-Yes activates YAP in 5-FU resistant quiescent colon cancer cells	[103]
	YAP activation causes resistance to 5-FU and docetaxel. YAP is overexpressed in resistant esophageal cancer tumors and 5-FU resistant cell lines.	YAP increases EGFR expression by binding to its promoter	[104]
	Cisplatin-resistant oral squamous cancer cell lines show decreased phospho-YAP and increased nuclear YAP. YAP knockdown causes increased sensitivity to cisplatin		[106]
	YAP activity correlates with cisplatin sensitivity of urothelial carcinoma cells. Nuclear YAP expression predicts poor outcome in urothelial carcinoma patients with chemotherapy	YAP knockdown causes increased DNA damage response and ATM activation upon cisplatin, accumulating DNA damages	[107]
	YAP and target gene expression are increased in cisplatin-resistant ovarian cancer cells, and YAP knockdown suppresses resistant cell viability	YAP induces increased autophagy by enhancing autolysosome degradation	[108]
Molecular targeted therapy	YAP amplification drives tumor maintenance against KRAS withdrawal in inducible KRAS mutant pancreatic ductal adenocarcinoma model	The YAP/TEAD complex cooperates with E2F to activate cell cycle and DNA replication programs	[109]
	YAP overexpression rescues KRAS mutant colon cancer cell lines from KRAS suppression	YAP induces epithelial-mesenchymal transition by interaction with FOS	[110]
	Combined YAP and RAF/MEK inhibition is synthetically lethal to BRAF or RAS-mutant tumors. Increased YAP expression is a biomarker of worse response to RAF/MEK inhibition in BRAF-mutant tumors	YAP induces the expression of Bcl-xL to antagonize anti-apoptotic signal	[113]
	BRAF inhibitor resistance of melanoma cells is dependent on YAP/TAZ activity, and inhibition of YAP/TAZ activation by actin modulation suppresses the resistance	Increased YAP/TAZ activity induces expression of E2F1-related cell cycle genes and activates EGFR, MYC, AKT	[114]
	YAP activation induces resistance to EGFR gefitinib in NSCLC cells. EGFR inhibitor resistant human NSCLC tumors show increased nuclear YAP staining compared with their pre-treatment tumors	YAP induces EMT, AXL expression, and ERK activation	[117]
	TAZ is upregulated in lung adenocarcinoma cells with EGFR T790 M mutation, and TAZ depletion sensitizes their response to gefitinib	TAZ depletion inhibits tumorigenicity, EMT, migration, and invasion of gefitinib-resistant NSCLC cells	[118]
	YAP activation signature is associated with poor response to cetuximab treatment in colorectal cancer patients		[119]
	High TAZ expression level is associated with poor response to trastuzumab in HER2-positive breast cancer patients		[120]
	YAP/TAZ inhibition diminishes matrix stiffness-dependent lapatinib resistance. Inhibition of YAP in tumor xenograft model slows the growth of HER2-amplified tumors and increases sensitivity to lapatinib	YAP and TAZ transduce resistant signals from rigid microenvironments	[121]
	Knockdown of YAP sensitizes ovarian cancer cells to cisplatin, EGFR inhibitor, and survivin inhibitor	PTPN14 downregulates YAP activity. PPXY motif containing PTPN14 fragment can sensitizes cancer cells to anti-cancer agents	[122]
Radiotherapy	YAP expression level in pre-treatment tumor tissue correlates with poor survival of head and neck squamous cell carcinoma patients		[123]
	YAP overexpression promotes medulloblastoma tumorigenesis, and promotes survival of cerebellar granule neuron precursors cells after irradiation	YAP enables cells to enter mitosis with un-repaired DNA through driving IGF2/AKT activation, resulting in ATM/Chk2 inactivation	[124]
	YAP knockdown in urothelial carcinoma cells increases DNA damage response induced by γ-irradiation	YAP knockdown causes increased DNA damage response and ATM activation, promoting accumulation of DNA damage	[107]