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

  • Victoria H. Cruz
  • Rolf A. BrekkenEmail author
Review

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.

Keywords

Autophagy Cancer therapeutic target Pancreatic cancer RAS TBK1 

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

Notes

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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Copyright information

© The International CCN Society 2017

Authors and Affiliations

  1. 1.Cancer Biology Graduate Program, Hamon Center for Therapeutic Oncology Research and Department of SurgeryUT Southwestern Medical CenterDallasUSA
  2. 2.Department of PharmacologyUT Southwestern Medical CenterDallasUSA

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