WWTR1

WWTR1
Identifiers
Aliases	WWTR1, TAZ, WW domain containing transcription regulator 1
External IDs	OMIM: 607392; MGI: 1917649; HomoloGene: 9159; GeneCards: WWTR1; OMA:WWTR1 - orthologs
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q25.1 Start 149,517,235 bp[1] End 149,736,714 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3|3 D Start 57,363,070 bp[2] End 57,483,331 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in tibia tail of epididymis optic nerve visceral pleura tendon of biceps brachii seminal vesicula urethra saphenous vein epithelium of colon lower lobe of lung Top expressed in left lung lobe right lung lobe atrioventricular valve dermis saccule vestibular sensory epithelium semi-lunar valve body of femur efferent ductule endothelial cell of lymphatic vessel More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein homodimerization activity transcription corepressor activity transcription coactivator activity protein binding Cellular component cytoplasm transcription regulator complex nucleoplasm nucleus cytosol nuclear body Biological process negative regulation of protein phosphorylation cilium assembly regulation of metanephric nephron tubule epithelial cell differentiation negative regulation of fat cell differentiation regulation of transcription, DNA-templated negative regulation of protein kinase activity multicellular organism growth regulation of canonical Wnt signaling pathway glomerulus development negative regulation of transcription by RNA polymerase II hippo signaling positive regulation of epithelial to mesenchymal transition regulation of SMAD protein signal transduction SCF-dependent proteasomal ubiquitin-dependent protein catabolic process mesenchymal cell differentiation stem cell division protein ubiquitination osteoblast differentiation kidney morphogenesis positive regulation of cell population proliferation transcription initiation from RNA polymerase II promoter negative regulation of canonical Wnt signaling pathway positive regulation of transcription by RNA polymerase II transcription, DNA-templated tissue homeostasis heart process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 25937 97064 Ensembl ENSG00000018408 ENSMUSG00000027803 UniProt Q9GZV5 Q9EPK5 RefSeq (mRNA) NM_001168278 NM_001168280 NM_015472 NM_001348362 NM_001168281 NM_133784 RefSeq (protein) NP_001161750 NP_001161752 NP_056287 NP_001335291 NP_001161753 NP_598545 Location (UCSC) Chr 3: 149.52 – 149.74 Mb Chr 3: 57.36 – 57.48 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

WW domain-containing transcription regulator protein 1 (WWTR1^[5]), also known as Transcriptional coactivator with PDZ-binding motif (TAZ), is a protein that in humans is encoded by the WWTR1 gene. WWTR1 acts as a transcriptional coregulator and has no effect on transcription alone.^[5] When in complex with transcription factor binding partners, WWTR1 helps promote gene expression in pathways associated with development, cell growth and survival, and inhibiting apoptosis.^[6] Aberrant WWTR1 function has been implicated for its role in driving cancers.^[7][8][9] WWTR1 is often referred to as TAZ due to its initial characterization with the name TAZ. However, WWTR1 (TAZ) is not to be confused with the protein tafazzin, which originally held the official gene symbol TAZ, and is now TAFAZZIN.

Structure

Protein structure of WWTR1 as predicted by AlphaFold.^[10]

Differences in binding domains present on transcriptional coregulators, YAP and TAZ.^[11]

WWTR1 contains a proline rich region, TEAD binding motif, WW domain, coiled coil region, and a transactivation domain (TAD) containing the PDZ domain-binding motif. WWTR1 (TAZ) lacks a DNA binding domain so it can not directly drive transcription. WWTR1 exhibits conserved structural homology with another transcriptional coregulator, yes-associated protein 1 (YAP).^[5] Both YAP and TAZ are able to form homodimers and heterodimers with each other through interactions at the coil coil domain.^[12] YAP and TAZ cooperate with transcription factors to promote tissue formation. WWTR1 (TAZ) interacts with a variety of transcriptional partners, including the four TEA domain family members (TEAD1/2/3/4) through the TEAD-binding motif and several other factors containing the PPXY motif, which consists of a Proline-Proline-X (any amino acid)-Tyrosine sequence. Examples of such partners include Runx/PEBP2, AP2, C/EBP, c-Jun, Krox-20, Krox-24, MEF2B, NF-E2, Oct-4 and p73, which interact with WWTR1 via the WW domain.^[6] The transactivation domain at the C-terminal end (amino acids 165–395) was shown to be important in producing transcriptional effects.^[6]

Function

WWTR1 (TAZ) and the structurally similar protein, YAP, act as transcriptional coactivators and are regulated by Hippo pathway activation.

WWTR1 (TAZ) plays an important role in embryogenesis and development,^[13][14] which include regulation of organ size,^[15][16][17] stem cell renewal,^[18] tissue regeneration,^[19][18] osteogenesis,^[20] and angiogenesis.^[21] These functions are effected through coactivation of transcription factors that promote cell growth, migration, and differentiation,^[15][16][17] such as the four members of the TEAD transcription factor family, Paired box gene 3 (PAX3), and Runt related transcription factors (RUNX1/)2).^[11] The proliferative functions of WWTR1 (TAZ) and its paralog, YAP, are restricted by the Hippo signaling pathway.^[22][23][24] This suppressive pathway consists of a kinase signaling cascade, the core of which is made up of the serine-threonine kinases, STK3/MST2 and STK4/MST1, which when active and complexed with the regulatory protein, SAV1, will phosphorylate and activate the LATS1/2 kinases, which in complex with the regulatory protein, MOB1, phosphorylate and downstream inactivate YAP/TAZ.^[14][15][25] In this way, Hippo activation arrests cell growth by decreasing proliferative gene expression, leading to decreased cell death by ferroptosis^[26][27] and increased cell death by apoptosis.^[14][15]

Functional redundancy with YAP

Similarities

WWTR1 (TAZ) has a similar structural sequence and binding motifs to yes-associated protein 1 (YAP).^[11] YAP and TAZ are often considered functionally redundant in existing literature.^[11] Both play roles in organ size development as well as cell migration, wound healing, angiogenesis, and metabolism, particularly in lipogenesis.^[11][28] Inactivation of YAP and TAZ occurs through phosphorylation by kinases in the Hippo pathway, namely LATS1 and LATS2.^[11] This recruits the binding of the regulatory protein, 14-3-3, which prevents YAP/TAZ from localizing to the nucleus and marks it for ubiquitination, which allows it to be recognized for subsequent degradation by proteasomes.^[11]

Differences

TAZ is able to form both heterodimers and heterotetramers with TEADs to initiate transcription (TAZ-TEAD and TAZ-TEAD-TAZ-TEAD), while YAP is only able to form YAP-TEAD heterodimers.^[11] These differences impart unique functions to TAZ, such as in the regulation of adipocyte differentiation through interactions with the peroxisome proliferator-activated receptor (PPARγ), as well as osteogenesis through transcriptional coactivation of bone-specific transcription factors, such as RUNX2 (also known as Cbfa1.)^[11] Additionally, TAZ independently interacts with Nuclear factor of activated T-cells 5 (NFATC5) in order to repress transcription in renal cells that are undergoing osmotic stress.^[11] Both YAP and TAZ associate with Mothers against decapentaplegic family transcription factors (SMAD) complexes to promote TGF-beta signaling and drive differentiation and development, but upregulation of only TAZ occurs upon transduction of this cascade.^[11] TAZ is only able to complex with SMAD2, SMAD3, or SMAD4 to promote nuclear shuttling and transcription, but YAP can also interact with SMAD1 and SMAD7 in addition.^[11] In vivo murine studies have demonstrated that animals lacking functional TAZ are more viable than animals lacking YAP expression.^[11] In contrast, silencing of YAP contributed to a more dramatic effect on cell expansion, glucose uptake, and cell cycle arrest than TAZ.^[11] When assayed in non-small-cell lung cancer (NSCLC) cell lines, WWTR1 maintained the extracellular matrix (ECM) organization and adhesion, and controlled migration more than YAP, which more closely regulated cell division and cell cycle progression genes.^[11]

Protein interactions

Binding of WWTR1 (TAZ) to transcription factors, such as TEAD, activates proliferative transcription.^[7][25]

WWTR1 (TAZ) function is inhibited when in complex with 14-3-3 binding protein.^[7][25]

Protein Interaction Partner	Functional Effects
AMOT, Angiomotin	Binding sequesters YAP/TAZ in the cytoplasm, inhibiting their function[12]
AP-1, Activator protein 1	Promoting trancsription[11]
ASPP2, Apoptosis-stimulating protein of p53	Promotes dephosphorylation and stabilization of WWTR1 (TAZ)[12]
β-catenin	Recruits a destruction complex that inactivates YAP/TAZ[12]
LATS1/LATS2, Large tumor suppressor kinases	Phosphorylation of WWTR1, marking it for ubiquination[11]
NFATC5, Nuclear factor of activated T-cells 5	Represses transcription in renal cells undergoing osmotic stress[11]
PF, Parafibromin	Stimulates WWTR1 (TAZ) function[12]
PAX3, Paired box gene 3	Promoting transcription[11]
PAX8 (Paired box gene 8) and NKX2-4 (NK homeobox)[25]	Coactivation of transcription factors involved in thyroid regulation[25]
PRRG4, Proline Rich And Gla Domain 4[25]	Suppressing transcription[11]
RUNX1/2, Runt related transcription factors	Promotes transcription[11]
SMAD2/3/4, Mothers against decapentaplegic family transcription factors	Nuclear shuttling; promoting transcription[11]
STAT1, Signal transducer and activator of transcription	Inhibiting STAT1/2 dimerization in metabolism[11]
TEAD1, TEA domain family member[25]	Transcriptional activation[11]
TEAD2, TEA domain family member,[25]
TEAD3, TEA domain family member,[25]
TEAD4, TEA domain family member[25]
YAP1, Yes-associated protein 1	Dimerization dependent transcriptional regulation[11]
YWHAE (14-3-3), Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein Epsilon[25]	Restricts WWTR1 translocation to the nucleus[5]
ZO-2, Tight junction protein 2	Localizes YAP/TAZ to the nucleus for increased activity[12]

Clinical significance

Roles in disease

WWTR1 has been implicated in many inflammatory diseases, including cancers.

Disease	Clinical Significance of WWTR1
Cancer	Associated with metastasis and poor survival prognosis across many cancer types[9]
Steatohepatitis	Overexpression of WWTR1 progresses simple steatosis to steatohepatitis by promoting fibrosis[29]
Atherosclerosis	Drives excessive endothelial cell proliferation and inflammation[30]
Sjogren Syndrome	Decreased WWTR1 localization to the nucleus results in lack of functional salivary/lacrimal gland development[14]
Hypertension	Activation of YAP/TAZ promotes glutamine metabolism and increases pulmonary blood pressure[31]
Psoriasis	YAP/TAZ activation drive pathologic angiogenesis and inflammation associated with chronic skin disorders[32]
Atopic Dermatitis
Rosacea
Chronic Urticaria

Cancers

WWTR1 (TAZ) is implicated a wide variety of cancers including melanoma, head and neck squamous cell carcinoma, breast cancer, non-small cell lung cancer, and others due to its high gene and histological expression, as well as correlation with increased metastasis and poorer survival in animal studies and patient data.^[9] Along with the structurally similar co-regulator YAP, many studies have described their role in promoting oncogenesis, altering neoplastic metabolism, and generating resistance to therapeutic intervention.^{[8][9][33][34]} In particular, TAZ overexpression conferred resistance to cisplatin chemotherapy as well as immunotherapy treatment with a PD-1 antibody.^[33]

Medium intensity WWTR1 protein expression in melanoma samples from Protein Atlas.

WWTR1 protein is expressed in moderate to high levels across a diverse array of cancer types and is associated with poor clinical outcomes.

WWTR1 Protein Expression By Cancer Type (from Protein Atlas)
Cancer Type	# Samples with Medium/High Expression	Total # Patient Samples	% Patient Samples with Medium/High Expression
Glioma	11	11	100%
Thyroid	4	4	100%
Lung	12	12	100%
Colorectal	11	11	100%
Head and Neck	4	4	100%
Liver	12	12	100%
Carcinoid	4	4	100%
Pancreatic	9	9	100%
Urothelial	9	9	100%
Prostate	10	10	100%
Testis	11	11	100%
Breast	12	12	100%
Cervical	9	9	100%
Endometrial	10	10	100%
Ovarian	11	11	100%
Melanoma	12	12	100%
Skin	11	11	100%
Stomach	10	11	90.1%
Renal	10	11	90.1%
Lymphoma	9	12	75%

As a drug target

YAP and TAZ function have been targeted in several therapeutic methods in the treatment of cancers.

The Hippo signaling agonist, C19, increases the phosphorylation of MST1/2 and LATS1/2, resulting in more downstream inactivation of YAP/TAZ. Modulating extracellular matrix stiffness and tension using thiazovivin, cucurbitacin I, dasatinib, fluvastatin, and pazopanib, exhibited positive results in breast cancer cell lines by preventing YAP/WWTR1 translocation to the nucleus.^[35] Endogenous hormonal factors that are synthesized for normal physiological functions such as epinephrine and glucagon have also been demonstrated to have similar inhibitory effects on YAP/TAZ function by promoting Hippo pathway activation.^[35] The class of cholesterol inhibitors, statins, was shown to inhibit the Rho family of GTP-ases (Rho-GTPase), which are enzymes that signal for upstream inhibition of the Hippo pathway, and exhibited similar effects in attenuating growth of breast cancer and human lung adenocarcinoma cells.^[35] Statins inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMG-CoA reductase), which is the precursor to mevalonate in the mevalonate pathway that synthesizes the lipid building blocks that form cholesterols and the lipid chains responsible for anchoring Rho-GTPases to the cell membrane.^[9] The Rho-GTPase, Ras Family Homolog A (RhoA), is activated by prenlylation (the posttranslational modification through addition of hydrophobic groups), and is responsible in part for modulating cytoskeletal elements that reduce Hippo pathway activity.^[9] By targeting Rho kinases with thiazovivin, or lipid synthesis through the mevalonate pathway, with statins, RhoA is inhibited and increased Hippo kinase activity may limit proliferation driven by YAP/TAZ.^[9][35] Tyrosine kinases signal in proliferative pathways, some which promote YAP/TAZ function, such as Src family kinases and includes the Yes tyrosine kinase, which is associated with YAP function. Targeting tyrosine kinases with inhibitors such as dasatinib and pazopanib has shown some effect in cancers.^[9]

Inhibition of YAP/TAZ function by targeting their interactions with their transcriptional partners in the TEAD family has also been studied.^[35][36] This includes the use of verteporfin, which was investigated in the treatment of skin cancers, particularly melanoma, although it was not taken beyond preclinical studies.^[35]

Drug/Molecule Name	Drug Class	Mechanism of Action
C19	Hippo kinase agonist	Increases phosphorylation by MST1/2 and LATS1/2 to inactivate YAP/TAZ and decrease cell proliferation[35]
Dihydrexidine	Dopamine agonist	Increases LATS1/2 activity; Decreases YAP/TAZ function and cell proliferation[35]
Epinephrine	Hormonal factor	Increases LATS1/2 activity; Decreases YAP/TAZ function and cell proliferation[35]
Glucagon	Hormonal factor
Thiazovivin	Rho kinase inhibitor	Inhibits Rho-GTPase; Increases LATS1/2 activity; Decreases YAP/TAZ function and cell proliferation[9][35]
Cucurbitacin I	JAK/STAT3 inhibitor
Dasatinib	Tyrosine kinase inhibitor
Fluvastatin	Statin
Pazopanib	Tyrosine kinase inhibitor
Verteporfin	TEAD inhibitor	Inhibits the binding of YAP/TAZ to TEAD family transcription factors; Decreases proliferative transcription and cell proliferation[35]

References

1. GRCh38: Ensembl release 89: ENSG00000018408 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027803 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Kanai F, Marignani PA, Sarbassova D, Yagi R, Hall RA, Donowitz M, et al. (December 2000). "TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins". The EMBO Journal. 19 (24): 6778–6791. doi:10.1093/emboj/19.24.6778. PMC 305881. PMID 11118213.
6. Hong W, Guan KL (September 2012). "The YAP and TAZ transcription co-activators: key downstream effectors of the mammalian Hippo pathway". Seminars in Cell & Developmental Biology. 23 (7): 785–793. doi:10.1016/j.semcdb.2012.05.004. PMC 3459069. PMID 22659496.
7. Moroishi T, Hansen CG, Guan KL (February 2015). "The emerging roles of YAP and TAZ in cancer". Nature Reviews. Cancer. 15 (2): 73–79. doi:10.1038/nrc3876. PMC 4562315. PMID 25592648.
8. Zhang X, Zhao H, Li Y, Xia D, Yang L, Ma Y, et al. (September 2018). "The role of YAP/TAZ activity in cancer metabolic reprogramming". Molecular Cancer. 17 (1): 134. doi:10.1186/s12943-018-0882-1. PMC 6122186. PMID 30176928.
9. Zanconato F, Cordenonsi M, Piccolo S (June 2016). "YAP/TAZ at the Roots of Cancer". Cancer Cell. 29 (6): 783–803. doi:10.1016/j.ccell.2016.05.005. PMC 6186419. PMID 27300434.
10. "AlphaFold Protein Structure Database". alphafold.ebi.ac.uk. Retrieved 2022-11-23.
11. Reggiani F, Gobbi G, Ciarrocchi A, Sancisi V (February 2021). "YAP and TAZ Are Not Identical Twins". Trends in Biochemical Sciences. 46 (2): 154–168. doi:10.1016/j.tibs.2020.08.012. PMID 32981815. S2CID 222166778.
12. Callus BA, Finch-Edmondson ML, Fletcher S, Wilton SD (February 2019). "YAPping about and not forgetting TAZ". FEBS Letters. 593 (3): 253–276. doi:10.1002/1873-3468.13318. PMID 30570758. S2CID 58578804.
13. Wu Z, Guan KL (January 2021). "Hippo Signaling in Embryogenesis and Development". Trends in Biochemical Sciences. 46 (1): 51–63. doi:10.1016/j.tibs.2020.08.008. PMC 7749079. PMID 32928629.
14. Zheng Y, Pan D (August 2019). "The Hippo Signaling Pathway in Development and Disease". Developmental Cell. 50 (3): 264–282. doi:10.1016/j.devcel.2019.06.003. PMC 6748048. PMID 31386861.
15. Piccolo S, Dupont S, Cordenonsi M (October 2014). "The biology of YAP/TAZ: hippo signaling and beyond". Physiological Reviews. 94 (4): 1287–1312. doi:10.1152/physrev.00005.2014. PMID 25287865.
16. Pocaterra A, Romani P, Dupont S (January 2020). "YAP/TAZ functions and their regulation at a glance". Journal of Cell Science. 133 (2): jcs230425. doi:10.1242/jcs.230425. hdl:11577/3317485. PMID 31996398. S2CID 210945848.
17. Totaro A, Panciera T, Piccolo S (August 2018). "YAP/TAZ upstream signals and downstream responses". Nature Cell Biology. 20 (8): 888–899. doi:10.1038/s41556-018-0142-z. PMC 6186418. PMID 30050119.
18. Moya IM, Halder G (April 2019). "Hippo-YAP/TAZ signalling in organ regeneration and regenerative medicine". Nature Reviews. Molecular Cell Biology. 20 (4): 211–226. doi:10.1038/s41580-018-0086-y. PMID 30546055. S2CID 54820180.
19. Driskill JH, Pan D (January 2021). "The Hippo Pathway in Liver Homeostasis and Pathophysiology". Annual Review of Pathology. 16: 299–322. doi:10.1146/annurev-pathol-030420-105050. PMC 8594752. PMID 33234023.
20. Kovar H, Bierbaumer L, Radic-Sarikas B (April 2020). "The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis". Cells. 9 (4): 972. doi:10.3390/cells9040972. PMC 7227004. PMID 32326412.
21. Boopathy GT, Hong W (2019). "Role of Hippo Pathway-YAP/TAZ Signaling in Angiogenesis". Frontiers in Cell and Developmental Biology. 7: 49. doi:10.3389/fcell.2019.00049. PMC 6468149. PMID 31024911.
22. Heng BC, Zhang X, Aubel D, Bai Y, Li X, Wei Y, et al. (January 2021). "An overview of signaling pathways regulating YAP/TAZ activity". Cellular and Molecular Life Sciences. 78 (2): 497–512. doi:10.1007/s00018-020-03579-8. PMC 11071991. PMID 32748155. S2CID 220930261.
23. Ma S, Meng Z, Chen R, Guan KL (June 2019). "The Hippo Pathway: Biology and Pathophysiology". Annual Review of Biochemistry. 88: 577–604. doi:10.1146/annurev-biochem-013118-111829. PMID 30566373. S2CID 58642425.
24. Meng Z, Moroishi T, Guan KL (January 2016). "Mechanisms of Hippo pathway regulation". Genes & Development. 30 (1): 1–17. doi:10.1101/gad.274027.115. PMC 4701972. PMID 26728553.
25. "UniProt - Q9GZV5 · WWTR1_HUMAN". www.uniprot.org. Retrieved 2022-11-17.
26. Sun T, Chi JT (May 2021). "Regulation of ferroptosis in cancer cells by YAP/TAZ and Hippo pathways: The therapeutic implications". Genes & Diseases. 8 (3): 241–249. doi:10.1016/j.gendis.2020.05.004. PMC 8093643. PMID 33997171.
27. Dai C, Chen X, Li J, Comish P, Kang R, Tang D (September 2020). "Transcription factors in ferroptotic cell death". Cancer Gene Therapy. 27 (9): 645–656. doi:10.1038/s41417-020-0170-2. PMID 32123318. S2CID 211728890.
28. Koo JH, Guan KL (August 2018). "Interplay between YAP/TAZ and Metabolism". Cell Metabolism. 28 (2): 196–206. doi:10.1016/j.cmet.2018.07.010. PMID 30089241. S2CID 51939438.
29. Kuchay MS, Choudhary NS, Mishra SK (2020-11-01). "Pathophysiological mechanisms underlying MAFLD". Diabetes & Metabolic Syndrome. 14 (6): 1875–1887. doi:10.1016/j.dsx.2020.09.026. PMID 32998095. S2CID 222166643.
30. Niu N, Xu S, Xu Y, Little PJ, Jin ZG (April 2019). "Targeting Mechanosensitive Transcription Factors in Atherosclerosis". Trends in Pharmacological Sciences. 40 (4): 253–266. doi:10.1016/j.tips.2019.02.004. PMC 6433497. PMID 30826122.
31. Zhang X, Zhao H, Li Y, Xia D, Yang L, Ma Y, et al. (September 2018). "The role of YAP/TAZ activity in cancer metabolic reprogramming". Molecular Cancer. 17 (1): 134. doi:10.1186/s12943-018-0882-1. PMC 6122186. PMID 30176928.
32. Lee HJ, Hong YJ, Kim M (November 2021). "Angiogenesis in Chronic Inflammatory Skin Disorders". International Journal of Molecular Sciences. 22 (21): 12035. doi:10.3390/ijms222112035. PMC 8584589. PMID 34769465.
33. Thompson BJ (May 2020). "YAP/TAZ: Drivers of Tumor Growth, Metastasis, and Resistance to Therapy". BioEssays. 42 (5): e1900162. doi:10.1002/bies.201900162. hdl:1885/211659. PMID 32128850. S2CID 212405819.
34. Zanconato F, Cordenonsi M, Piccolo S (August 2019). "YAP and TAZ: a signalling hub of the tumour microenvironment". Nature Reviews. Cancer. 19 (8): 454–464. doi:10.1038/s41568-019-0168-y. PMID 31270418. S2CID 195791034.
35. Andl T, Zhou L, Yang K, Kadekaro AL, Zhang Y (June 2017). "YAP and WWTR1: New targets for skin cancer treatment". Cancer Letters. 396: 30–41. doi:10.1016/j.canlet.2017.03.001. PMID 28279717.
36. Pobbati AV, Hong W (2020). "A combat with the YAP/TAZ-TEAD oncoproteins for cancer therapy". Theranostics. 10 (8): 3622–3635. doi:10.7150/thno.40889. PMC 7069086. PMID 32206112.