Advances of targeting the YAP/TAZ-TEAD complex in the hippo pathway for the treatment of cancers

doi:10.1016/j.ejmech.2022.114847

Review

. 2022 Dec 15:244:114847.

doi: 10.1016/j.ejmech.2022.114847. Epub 2022 Oct 13.

Advances of targeting the YAP/TAZ-TEAD complex in the hippo pathway for the treatment of cancers

Mengxin Luo¹, Yongjin Xu², Haifeng Chen³, Yiquan Wu³, Ao Pang³, Junjie Hu⁴, Xiaowu Dong⁵, Jinxin Che⁶, Haiyan Yang⁷

Affiliations

¹ Department of Lymphoma, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, PR China; Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
² Department of Lymphoma, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, PR China.
³ Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
⁴ Women's Hospital, School of Medicine Zhejiang University, Hangzhou, China.
⁵ Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China; Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Hangzhou, 310018, PR China; Cancer Center, Zhejiang University, Hangzhou, 310058, PR China.
⁶ Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China. Electronic address: chejx@zju.edu.cn.
⁷ Department of Lymphoma, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, PR China. Electronic address: yanghy@zjcc.org.cn.

PMID: 36265280
DOI: 10.1016/j.ejmech.2022.114847

Review

Advances of targeting the YAP/TAZ-TEAD complex in the hippo pathway for the treatment of cancers

Mengxin Luo et al. Eur J Med Chem. 2022.

. 2022 Dec 15:244:114847.

doi: 10.1016/j.ejmech.2022.114847. Epub 2022 Oct 13.

Authors

Mengxin Luo¹, Yongjin Xu², Haifeng Chen³, Yiquan Wu³, Ao Pang³, Junjie Hu⁴, Xiaowu Dong⁵, Jinxin Che⁶, Haiyan Yang⁷

Affiliations

¹ Department of Lymphoma, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, PR China; Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
² Department of Lymphoma, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, PR China.
³ Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
⁴ Women's Hospital, School of Medicine Zhejiang University, Hangzhou, China.
⁵ Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China; Innovation Institute for Artificial Intelligence in Medicine of Zhejiang University, Hangzhou, 310018, PR China; Cancer Center, Zhejiang University, Hangzhou, 310058, PR China.
⁶ Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China. Electronic address: chejx@zju.edu.cn.
⁷ Department of Lymphoma, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, PR China. Electronic address: yanghy@zjcc.org.cn.

PMID: 36265280
DOI: 10.1016/j.ejmech.2022.114847

Abstract

The Hippo pathway is an evolutionarily conserved signaling pathway that plays critical roles in the tumorigenesis and progression of breast cancer, oral cancer, rectal cancer, colloid cancer, and so on. YAP/TAZ-TEAD complex is a key knot in the Hippo pathway regulating cell proliferation and stem cell functions. Activation or overexpression of this complex has been proved to lead to cell transformation, proliferation and eventually cancerization. In this review, the association between the alterations of hippo pathway and tumorigenesis of various cancer had been elucidated. The structural basis of YAP/TAZ-TEAD complex is analyzed, and the targeting inhibitors are summarized within the medicinal chemistry classification. Moreover, we have also discussed the clinical status and current challenges of these drug candidates, and provide guidance for the future development of inhibitors targeting this pathway, especially YAP/TAZ-TEAD complex.

Keywords: Cancers; Hippo pathway; Palmitoyl pocket; Targeting inhibitors; YAP/TAZ-TEAD complex.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Cited by

The oncogenic roles and clinical implications of YAP/TAZ in breast cancer.
Luo J, Zou H, Guo Y, Tong T, Chen Y, Xiao Y, Pan Y, Li P. Luo J, et al. Br J Cancer. 2023 May;128(9):1611-1624. doi: 10.1038/s41416-023-02182-5. Epub 2023 Feb 9. Br J Cancer. 2023. PMID: 36759723 Free PMC article. Review.
TAZ upregulates MIR-224 to inhibit oxidative stress response in multiple myeloma.
Abegunde SO, Grieve S, Reiman T. Abegunde SO, et al. Cancer Rep (Hoboken). 2023 Oct;6(10):e1879. doi: 10.1002/cnr2.1879. Epub 2023 Aug 4. Cancer Rep (Hoboken). 2023. PMID: 37539777 Free PMC article.
New insights into the ambivalent role of YAP/TAZ in human cancers.
Luo J, Deng L, Zou H, Guo Y, Tong T, Huang M, Ling G, Li P. Luo J, et al. J Exp Clin Cancer Res. 2023 May 22;42(1):130. doi: 10.1186/s13046-023-02704-2. J Exp Clin Cancer Res. 2023. PMID: 37211598 Free PMC article. Review.
Computational design and experimental confirmation of a disulfide-stapled YAP helix^α1-trap derived from TEAD4 helical hairpin to selectively capture YAP α1-helix with potent antitumor activity.
Li K, Liu L. Li K, et al. J Comput Aided Mol Des. 2024 Aug 23;38(1):31. doi: 10.1007/s10822-024-00572-2. J Comput Aided Mol Des. 2024. PMID: 39177727
Activin and BMP Signalling in Human Testicular Cancer Cell Lines, and a Role for the Nucleocytoplasmic Transport Protein Importin-5 in Their Crosstalk.
Radhakrishnan K, Luu M, Iaria J, Sutherland JM, McLaughlin EA, Zhu HJ, Loveland KL. Radhakrishnan K, et al. Cells. 2023 Mar 24;12(7):1000. doi: 10.3390/cells12071000. Cells. 2023. PMID: 37048077 Free PMC article.

See all "Cited by" articles

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
- Elsevier Science

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Advances of targeting the YAP/TAZ-TEAD complex in the hippo pathway for the treatment of cancers

Affiliations

Advances of targeting the YAP/TAZ-TEAD complex in the hippo pathway for the treatment of cancers

Authors

Affiliations

Abstract

Conflict of interest statement

Similar articles

Cited by

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Abstract

Conflict of interest statement

Similar articles

Cited by

Publication types

MeSH terms

Substances

Related information

LinkOut - more resources

Full Text Sources