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Non-hippo kinases: indispensable roles in YAP/TAZ signaling and implications in cancer therapy

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Abstract

The transcriptional co-activators Yes-associated protein (YAP) and PDZ-binding domain (TAZ) are the known downstream effectors of the Hippo kinase cascade. YAP/TAZ have been shown to play important roles in cellular growth and differentiation, tissue development and carcinogenesis. Recent studies have found that, in addition to the Hippo kinase cascade, multiple non-Hippo kinases also regulate the YAP/TAZ cellular signaling and produce important effects on cellular functions, particularly on tumorigenesis and progression. In this article, we will review the multifaceted regulation of the YAP/TAZ signaling by the non-Hippo kinases and discuss the potential application of the non-Hippo kinase-regulated YAP/TAZ signaling for cancer therapy.

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Abbreviations

ALL:

Acute lymphoblastic leukemia

AMPK:

AMP-activated protein kinase

CCA:

Cholangiocarcinoma

CDK:

Cyclin-dependent kinase

CK1:

Casein kinase 1

CML:

Chronic myeloid leukemia

EGFR:

Epidermal growth factor receptor

GBM:

Glioblastoma

GSK3:

Glycogen synthase kinase 3

HCC:

Hepatocellular carcinoma

HNSCC:

Head and neck squamous cell carcinomas

IHC:

Immunohistochemistry

IKK:

IκB kinase

LATS1/2:

Large tumor suppressor kinase 1/2

LKB1:

Liver kinase B1

MAP4Ks:

Mitogen-activated protein kinase kinase kinase kinases

MAPKs:

Mitogen-activated protein kinases

MOB1:

Mps one binder kinase activator 1

MPM:

Malignant pleural mesothelioma

MST1/2:

Mammalian Ste20-like kinase 1/2

mTOR:

Mammalian target of rapamycin

NDR1/2:

Nuclear Dbf2-related kinase 1/2

NGF:

Nerve growth factor

NF-κB:

Nuclear factor-κB

NLK:

Nemo-like kinase

NSCLC:

Non-small cell lung cancer

NTRK1:

Neurotrophic receptor tyrosine kinase 1

PDGFR:

Platelet derived growth factor receptor

PDK1:

3-phosphoinositide-dependent protein kinase-1

PDX:

Patient-derived xenograft

Ph +:

Philadelphia chromosome-positive

ROCK1/2:

Rho-associated protein kinase 1 and 2

RTK:

Receptor tyrosine kinase

SAV1:

Salvador homologue 1

SFK:

Src family tyrosine kinase

SH3:

Src homology domain 3

STK38:

Serine/threonine kinase 38

TCF/LEF:

T-cell factor/lymphoid enhancer factor

TEADs:

TEA domain family members

TFIIH:

Transcriptional initiation factor II-H

TKI:

Tyrosine kinase inhibitor

TNBC:

Triple-negative breast cancer

UPS:

Ubiquitin-proteasome system

VGLL4:

Vestigial-like protein 4

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Acknowledgements

We thank Wannian Yang for very helpful discussions and critical reading of this manuscript. We apologize for not being able to include some original work due to space constraints.

Funding

This work was supported by grants from the National Natural Science Foundation of China (81372208 and 81871888).

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  1. School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, China

    Jun Zhu, Tiantian Wu & Qiong Lin

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  1. Jun Zhu
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JZ, TW and QL designed and organized the manuscript. JZ wrote the manuscript and prepared the figures. TW reviewed and edited the manuscript. JZ, WT and QL finalized the manuscript. All authors read and approved the final manuscript.

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Correspondence to Qiong Lin.

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Zhu, J., Wu, T. & Lin, Q. Non-hippo kinases: indispensable roles in YAP/TAZ signaling and implications in cancer therapy. Mol Biol Rep 50, 4565–4578 (2023). https://doi.org/10.1007/s11033-023-08329-0

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