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Assessment of TANK-binding kinase 1 as a therapeutic target in cancer

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  • Published:
Journal of Cell Communication and Signaling

Abstract

TANK-binding kinase 1 (TBK1) is central to multiple biological processes that promote tumorigenesis including cell division, autophagy, innate immune response and AKT-pro survival signaling. TBK1 is well studied and most known for its function in innate immunity. However, the serine threonine protein kinase received significant attention as a synthetic lethal partner and effector of the major oncogene, RAS. This review summarizes newly identified cancer promoting functions of TBK1 and evaluates the therapeutic potential of targeting TBK1 in cancer.

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Abbreviations

AALE:

Immortalized tracheobronchial epithelial cells

AKT:

Protein kinase B

BRAFi:

BRAF inhibitor

CCL5:

Chemokine ligand 5

CEP1:

Centrosomal protein 170

DC:

Dendritic cell

DKO:

Dendritic cell knockout

EMT:

Epithelial-to-mesenchymal transition

GEMM:

Genetically engineered mouse model

GFP:

Green fluorescent protein

IFN-I:

Type I interferon

IFN-β:

Interferon β

IFNAR1:

Interferon alpha/beta receptor 1

IKB:

Inhibitor of NFκβ

IKK:

Iκβ kinase

IL1:

Interleukin 1

IL6:

Interleukin 6

IRF3:

Interferon regulator factor 3

LATS1:

Large tumor suppressor kinase 1

LC3:

Microtubule-associated protein-1 light chain 3

MEFs:

Mouse embryonic fibroblasts

MEKi:

MEK inhibitor

mTOR:

Mammalian target of rapamycin

NFκβ:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NSCLC:

Non-small cell lung cancer

NSG:

NOD scid gamma

NUMA:

Nuclear mitotic apparatus protein

OPTN:

Optineurin

PD-1:

Programmed cell death protein 1

PDA:

Pancreatic ductal adenocarcinoma

PDK1:

3-phosphoinositide-dependent protein kinase-1

PLK1:

Polo-like kinase 1

RAL:

Ras-related protein

RAS:

Rat sarcoma virus

S6K:

p70 S6 kinase

SILAC:

Stable isotope labeling by amino acids in cell culture

siRNA:

Small interfering RNA

STAT3:

Signal transducer and activator of transcription 3

STING:

Stimulator of interferon genes

TANK:

TRAF family member associated NF-κβ activator

TBK1:

TANK -binding kinase 1

TBK1i:

TBK1 inhibitor

TCGA:

The cancer genome atlas

TGFB:

Transforming growth factor β

WT:

Wild-type

YAP1:

Yes associated protein 1

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Acknowledgements

The authors thank Drs. Jonathan Cooper and Aubhishek Zaman for many helpful discussions and members of the Brekken lab for critical review of this manuscript. We also gratefully acknowledge Dr. Tae Hyun Hwang for his help with TCGA gene expression analysis and Dave Primm for editorial assistance.

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Authors and Affiliations

  1. Cancer Biology Graduate Program, Hamon Center for Therapeutic Oncology Research and Department of Surgery, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX, 75390-8593, USA

    Victoria H. Cruz & Rolf A. Brekken

  2. Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX, USA

    Rolf A. Brekken

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  1. Victoria H. Cruz
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Correspondence to Rolf A. Brekken.

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Cruz, V.H., Brekken, R.A. Assessment of TANK-binding kinase 1 as a therapeutic target in cancer. J. Cell Commun. Signal. 12, 83–90 (2018). https://doi.org/10.1007/s12079-017-0438-y

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