Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ASCO Annual Meeting 2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

2024 ASCO Annual Meeting

Keep up to date with all the top stories and latest evidence with our hub page, including official congress videos and expert takeaways.
ADVANCED SEARCH
Log in
Top
Cancer and Metastasis Reviews
Published in: Cancer and Metastasis Reviews 1/2014

01-03-2014 | NON-THEMATIC REVIEW

The dual functions of YAP-1 to promote and inhibit cell growth in human malignancy

Authors: Hai Wang, Yu-Chen Du, Xiao-jun Zhou, Hong Liu, Shou-Ching Tang

Published in: Cancer and Metastasis Reviews | Issue 1/2014

Login to get access

Abstract

The major functions of Hippo (Hpo) signaling pathway are to control cell growth, proliferation, and apoptosis. As its important downstream player, yes-associated protein (YAP)-1 was originally found to promote cell proliferation and transformation. Overexpression of YAP-1 has been linked to tumor progression and worse survival in certain malignancies. However, it has been recently recognized as a tumor suppressor gene as well since it also induces apoptosis. Decreased or absent expression of YAP-1 is highly correlated with tumor progression and worse survival in other tumors such as breast cancer. It is clear that YAP-1 plays a dual role as oncogene and tumor suppressor gene in human oncogenesis, depending on the specific tissue type involved. Here, we reviewed the recent research on both the oncogenic and tumor suppressor function of YAP-1 and its significance in human malignancy. The clinical implication of YAP-1 expression in cancer prognosis and the development of targeted therapy will also be discussed.
Literature
1.
Zhao, B., et al. (2013). The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal. Nature Cell Biology, 13, 877–883.CrossRef
2.
Zhou, D., et al. (2011). Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance. Proceedings of the National Academy of Sciences of the United States of America, 108, E1312–E1320.PubMedCrossRefPubMedCentral
3.
Tamm, C., et al. (2011). Regulation of mouse embryonic stem cell self-renewal by a Yes-YAP-TEAD2 signaling pathway downstream of LIF. Journal of Cell Science, 124, 1136–1144.PubMedCrossRef
4.
Zhang, H., et al. (2011). Yes-associated protein (YAP) transcriptional coactivator functions in balancing growth and differentiation in skin. Proceedings of the National Academy of Sciences of the United States of America, 108, 2270–2275.PubMedCrossRefPubMedCentral
5.
6.
Zhao, B., et al. (2007). Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. Genes and Development, 21, 2747–2761.PubMedCrossRefPubMedCentral
7.
Lapi, E., et al. (2008). PML, YAP, and p73 are components of a proapoptotic autoregulatory feedback loop. Molecular Cell, 32, 803–814.PubMedCrossRef
8.
Strano, S., et al. (2007). The transcriptional coactivator Yes-associated protein drives p73 gene-target specificity in response to DNA damage. Molecular Cell, 18, 447–459.CrossRef
9.
Yuan, M., et al. (2008). Yes-associated protein (YAP) functions as a tumor suppressor in breast. Cell Death and Differentiation, 15, 1752–1759.PubMedCrossRef
10.
Bertini, E. (2009). YAP: at the crossroad between transformation and tumor suppression. Cell Cycle, 8, 49–57.PubMedCrossRef
11.
Zender, L., et al. (2006). Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach. Cell, 125, 1253–1267.PubMedCrossRefPubMedCentral
12.
Overholtzer, M., et al. (2006). Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon. Proceedings of the National Academy of Sciences of the United States of America, 103, 12405–12410.PubMedCrossRefPubMedCentral
13.
14.
15.
Hao, Y., et al. (2008). Tumor suppressor LATS1 is a negative regulator of oncogene YAP. Journal of Biological Chemistry, 283, 5496–5509.PubMedCrossRef
16.
Oka, T., et al. (2008). Mst2 and Lats kinases regulate apoptotic function of Yes kinase-associated protein (YAP). Journal of Biological Chemistry, 283, 27534–27546.PubMedCrossRef
17.
Ren, F. L., et al. (2010). Hippo signaling regulates Yorkie nuclear localization and activity through 14-3-3 dependent and independent mechanisms. Developmental Biology, 337, 303–312.PubMedCrossRefPubMedCentral
18.
Zhao, B., et al. (2010). A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP). Genes and Development, 24, 72–85.PubMedCrossRefPubMedCentral
19.
Basu, S., et al. (2003). Akt phosphorylates the Yes-associated protein, YAP, to induce interaction with 14-3-3 and attenuation of p73-mediated apoptosis. Molecular Cell, 11, 11–23.PubMedCrossRef
20.
21.
Oka, T., et al. (2010). Functional complexes between YAP2 and ZO-2 are PDZ domain-dependent, and regulate YAP2 nuclear localization and signalling. The Biochemical Journal, 432, 461–472.PubMedCrossRef
22.
Remue, E., et al. (2010). TAZ interacts with zonula occludens-1 and -2 proteins in a PDZ-1 dependent manner. FEBS Letters, 584, 4175–4180.PubMedCrossRef
23.
Wu, S., et al. (2003). Hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts. Cell, 114, 445–456.PubMedCrossRef
24.
Harvey, K. F., et al. (2003). The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis. Cell, 114, 457–467.PubMedCrossRef
25.
Callus, B. A., et al. (2006). Association of mammalian sterile twenty kinases, Mst1 and Mst2, with hSalvador via C-terminal coiled-coil domains, leads to its stabilization and phosphorylation. The FEBS Journal, 273, 4264–4276.PubMedCrossRef
26.
Chan, E. H., et al. (2005). Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1. Oncogene, 24, 2076–2086.PubMedCrossRef
27.
Praskova, M., et al. (2008). MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation. Current Biology: CB, 18, 311–321.PubMedCrossRef
28.
Oka, T. V., et al. (2008). Mst2 and Lats kinases regulate apoptotic function of Yes kinase-associated protein (YAP). Journal of Biological Chemistry, 283, 27534–27546.PubMedCrossRef
29.
Zhang, L., et al. (2008). The TEAD/TEF family of transcription factor Scalloped mediates Hippo signaling in organ size control. Developmental Cell, 14, 377–387.PubMedCrossRefPubMedCentral
30.
Wu, S., et al. (2008). The TEAD/TEF family protein Scalloped mediates transcriptional output of the Hippo growth-regulatory pathway. Developmental Cell, 14(2008), 388–398.PubMedCrossRef
31.
32.
Neto-Silva, R. M., et al. (2010). Evidence for a growth-stabilizing regulatory feedback mechanism between Myc and Yorkie, the Drosophila homolog of Yap. Developmental Cell, 19, 507–520.PubMedCrossRefPubMedCentral
33.
Zhang, J., et al. (2009). YAP-dependent induction of amphiregulin identifies a non-cell-autonomous component of the Hippo pathway. Nature Cell Biology, 11, 1444–1450.PubMedCrossRefPubMedCentral
34.
35.
Vitolo, M. I., et al. (2007). The RUNX2 transcription factor cooperates with the YES-associated protein, YAP65, to promote cell transformation. Cancer Biology & Therapy, 6, 856–863.CrossRef
36.
Komuro, A., et al. (2003). WW domain-containing protein YAP associates with ErbB-4 and acts as a co-transcriptional activator for the carboxyl-terminal fragment of ErbB-4 that translocates to the nucleus. Journal of Biological Chemistry, 278, 33334–33341.
37.
Strano, S., et al. (2001). Physical interaction with Yes-associated protein enhances p73 transcriptional activity. Journal of Biological Chemistry, 276, 15164–15173.PubMedCrossRef
38.
Lamar, J. M., et al. (2012). The Hippo pathway target, YAP, promotes metastasis through its TEAD-interaction domain. Proceedings of the National Academy of Sciences of the United States of America, 109, E2441–E2450.PubMedCrossRefPubMedCentral
39.
Xu, M. Z., et al. (2011). AXL receptor kinase is a mediator of YAP-dependent oncogenic functions in hepatocellular carcinoma. Oncogene, 30, 1229–1240.PubMedCrossRefPubMedCentral
40.
Ehsanian, R., et al. (2010). YAP dysregulation by phosphorylation or DeltaNp63-mediated gene repression promotes proliferation, survival and migration in head and neck cancer subsets. Oncogene, 29, 6160–6171.PubMedCrossRefPubMedCentral
41.
Yu,S.J., et al. (2013). MicroRNA-200a promotes anoikis resistance and metastasis by targeting YAP1 in human breast cancer. Clinical Cancer Research, 19, 1389–1399.
42.
Espanel, X., et al. (2001). Yes-associated protein and p53-binding protein-2 interact through their WW and SH3 domains. Journal of Biological Chemistry, 276, 14514–14523.PubMed
43.
Danovi, S. A., et al. (2008). Yes-associated protein (YAP) is a critical mediator of c-Jun-dependent apoptosis. Cell Death and Differentiation, 15, 217–219.PubMedCrossRef
44.
Levy, D., et al. (2008). Yap1 phosphorylation by c-Abl is a critical step in selective activation of proapoptotic genes in response to DNA damage. Molecular Cell, 29, 350–361.PubMedCrossRef
45.
Levy, D., et al. (2007). The Yes-associated protein 1 stabilizes p73 by preventing Itch-mediated ubiquitination of p73. Cell Death and Differentiation, 14, 743–751.
46.
Okazaki, T., et al. (2012). Up-regulation of endogenous PML induced by a combination of interferon-beta and temozolomide enhances p73/YAP-mediated apoptosis in glioblastoma. Cancer Letters, 323, 199–207.PubMedCrossRef
47.
Yee, K.S., et al. (2012). A RASSF1A polymorphism restricts p53/p73 activation and associates with poor survival and accelerated age of onset of soft tissue sarcoma. Cancer Research, 72, 2206–2217.
48.
Matallanas, D., et al. (2007). RASSF1A elicits apoptosis through an MST2 pathway directing proapoptotic transcription by the p73 tumor suppressor protein. Molecular Cell, 27, 962–975.PubMedCrossRefPubMedCentral
49.
Camargo, F. D., et al. (2007). YAP1 increases organ size and expands undifferentiated progenitor cells. Current Biology, 17(23), 2054–2060.PubMedCrossRef
50.
Lian, I., et al. (2010). The role of YAP transcription coactivator in regulating stem cell self-renewal and differentiation. Genes & Development, 24(11), 1106–1118.CrossRef
51.
Zhou, D., et al. (2011). Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance. Proceedings of the National Academy of Sciences of the United States of America, 108(49), E1312–E1320.PubMedCrossRefPubMedCentral
52.
Varelas, X., et al. (2010). The Crumbs complex couples cell density sensing to Hippo-dependent control of the TGF-beta-SMAD pathway. Developmental Cell, 19, 831–844.PubMedCrossRef
53.
54.
Fan, R., et al. (2013). Regulation of Hippo pathway by mitogenic growth factors via phosphoinositide 3-kinase and phosphoinositide-dependent kinase-1. Proceedings of the National Academy of Sciences of the United States of America, 110(7), 2569–2574.PubMedCrossRefPubMedCentral
55.
Fernandez, L. A., et al. (2009). YAP1 is amplified and up-regulated in hedgehog-associated medulloblastomas and mediates Sonic hedgehog-driven neural precursor proliferation. Genes and Development, 23, 2729–2741.CrossRef
56.
Tumaneng, K., et al. (2012). YAP mediates crosstalk between the Hippo and PI(3)K-TOR pathways by suppressing PTEN via miR-29. Nature Cell Biology, 14, 1322–1329.PubMedCrossRef
57.
Rosenbluh, J., et al. (2012). â-Catenin-driven cancers require a YAP1 transcriptional complex for survival and tumorigenesis. Cell, 151(7), 1457–1473.PubMedCrossRefPubMedCentral
58.
Tschaharganeh, D. F., et al. (2013). Yes-associated protein up-regulates Jagged-1 and activates the Notch pathway in human hepatocellular carcinoma. Gastroenterology, 144(7), 1530–1542.PubMedCrossRef
59.
Muramatsu, T., et al. (2011). YAP is a candidate oncogene for esophageal squamous cell carcinoma. Carcinogenesis, 32, 389–398.PubMedCrossRef
60.
Imoto, I., et al. (2001). Identification of cIAP1 as a candidate target gene within an amplicon at 11q22 in esophageal squamous cell carcinomas. Cancer Research, 61, 6629–6634.PubMed
61.
Liu, T., et al. (2013). Clinical significance of yes-associated protein overexpression in cervical carcinoma: the differential effects based on histotypes. International Journal of Gynecological Cancer, 23, 735–742.PubMedCrossRef
62.
Tang, S.C., et al. (2002). BAG-1, an anti-apoptotic tumour marker. IUBMB Life, 53, 99–105.
63.
Tang, S. C., et al. (1999). Expression of BAG-1 in invasive breast carcinomas. Journal of Clinical Oncology, 17, 1710–1719.PubMed
64.
Turner, B. C., et al. (2001). BAG-1: a novel biomarker predicting long-term survival in early-stage breast cancer. Journal of Clinical Oncology, 19, 992–1000.PubMed
65.
66.
Song, M., et al. (2012). Nuclear expression of Yes-associated protein 1 correlates with poor prognosis in intestinal type gastric cancer. Anticancer Research, 32, 3827–3834.PubMed
67.
Wang, Y., et al. (2010). Overexpression of yes-associated protein contributes to progression and poor prognosis of non-small-cell lung cancer. Cancer Science, 101, 1279–1285.PubMedCrossRef
68.
Su, L. L., et al. (2012). Expression of Yes-associated protein in non-small cell lung cancer and its relationship with clinical pathological factors. Chinese Medical Journal, 125, 4003–4008.PubMed
69.
Carter, S. L., et al. (1994). Loss of heterozygosity at 11q22-q23 in breast cancer. Cancer Research, 54, 6270–6274.PubMed
70.
Winqvist, R., et al. (1995). Loss of heterozygosity for chromosome 11 in primary human breast tumors is associated with poor survival after metastasis. Cancer Research, 55, 2660–2664.PubMed
71.
Gudmundsson, J., et al. (1995). Loss of heterozygosity at chromosome 11 in breast cancer: association of prognostic factors with genetic alterations. British Journal of Cancer, 72, 696–701.PubMedCrossRefPubMedCentral
72.
Hampton, G. M., et al. (1994). Loss of heterozygosity in sporadic human breast carcinoma: a common region between 11q22 and 11q23.3. Cancer Research, 54, 4586–4589.PubMed
73.
74.
Tufail, R., et al. (2012). Loss of Yes-associated protein (YAP) expression is associated with estrogen and progesterone receptors negativity in invasive breast carcinomas. Breast Cancer Research and Treatment, 131, 743–750.PubMedCrossRefPubMedCentral
75.
Wang, Y., et al. (2013). Clinical and prognostic significance of Yes-associated protein in colorectal cancer. Tumour Biology, 34(4), 2169–2174.PubMedCrossRef
76.
Fujii, M., et al. (2012). Exploration of a new drug that targets YAP. Journal of Biochemistry, 152(3), 209–211.PubMedCrossRef
77.
Bao, Y., et al. (2011). A cell-based assay to screen stimulators of the Hippo pathway reveals the inhibitory effect of dobutamine on the YAP-dependent gene transcription. Journal of Biochemistry, 150(2), 199–208.PubMedCrossRef
Metadata
Title
The dual functions of YAP-1 to promote and inhibit cell growth in human malignancy
Authors
Hai Wang
Yu-Chen Du
Xiao-jun Zhou
Hong Liu
Shou-Ching Tang
Publication date
01-03-2014
Publisher
Springer US
Published in
Cancer and Metastasis Reviews / Issue 1/2014
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI
https://doi.org/10.1007/s10555-013-9463-3

Other articles of this Issue 1/2014

Cancer and Metastasis Reviews 1/2014 Go to the issue

NON-THEMATIC REVIEW

Emerging evidence for CHFR as a cancer biomarker: from tumor biology to precision medicine

EditorialNotes

Gastroenteropancreatic neuroendocrine tumors: current perspectives and future challenges

Clinical

Why anti-Bcl-2 clinical trials fail: a solution

NON-THEMATIC REVIEW

Ribosomal proteins as novel players in tumorigenesis

Clinical

Adoptive immunotherapy of metastatic breast cancer: present and future

NON-THEMATIC REVIEW

GAP-independent functions of DLC1 in metastasis

2024 ASCO Annual Meeting Coverage

Highlights of the Day: Breast cancer – metastatic

Breast Cancer Video

In this session, Dr. Wolff provides his key takeaways from the data presented in the metastatic breast cancer oral abstract session at ASCO 2024.

Watch now

Highlights of the Day: Gynecologic cancer

Gynecologic Cancer Video

Highlights of the Day: Breast Cancer – local/regional/adjuvant

Breast Cancer Video

Neoadjuvant dual immunotherapy improves melanoma outcomes

04-06-2024 Melanoma News

» View more highlights on the ASCO 2024 congress hub page

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits