Inhibition of PLK4 remodels histone methylation and activates the immune response via the cGAS-STING pathway in TP53-mutated AML

2.

Daver

NG

,

Maiti

A

,

Kadia

TM

, et al.

TP53-mutated myelodysplastic syndrome and acute myeloid leukemia: biology, current therapy, and future directions

.

Cancer Discov

.

2022

;

12

(

11

):

2516

-

2529

.

3.

Welch

JS

,

Petti

AA

,

Miller

CA

, et al.

TP53 and decitabine in acute myeloid leukemia and myelodysplastic syndromes

.

N Engl J Med

.

2016

;

375

(

21

):

2023

-

2036

.

4.

Sallman

DA

,

DeZern

AE

,

Garcia-Manero

G

, et al.

Eprenetapopt (APR-246) and azacitidine in TP53-mutant myelodysplastic syndromes

.

J Clin Oncol

.

2021

;

39

(

14

):

1584

-

1594

.

5.

Sallman

DA

,

Al Malki

M

,

Asch

AS

, et al.

Tolerability and efficacy of the first-in-class anti-CD47 antibody magrolimab combined with azacitidine in MDS and AML patients: Phase Ib results

.

J Clin Oncol

.

2020

;

38

(

15_suppl

):

7507

.

6.

Zitouni

S

,

Nabais

C

,

Jana

SC

,

Guerrero

A

,

Bettencourt-Dias

M

.

Polo-like kinases: structural variations lead to multiple functions

.

Nat Rev Mol Cell Biol

.

2014

;

15

(

7

):

433

-

452

.

7.

Press

MF

,

Xie

B

,

Davenport

S

, et al.

Role for polo-like kinase 4 in mediation of cytokinesis

.

Proc Natl Acad Sci U S A

.

2019

;

116

(

23

):

11309

-

11318

.

8.

Puklowski

A

,

Homsi

Y

,

Keller

D

, et al.

The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to control centrosome duplication

.

Nat Cell Biol

.

2011

;

13

(

8

):

1004

-

1009

.

9.

Ohta

M

,

Ashikawa

T

,

Nozaki

Y

, et al.

Direct interaction of Plk4 with STIL ensures formation of a single procentriole per parental centriole

.

Nat Commun

.

2014

;

5

:

5267

.

10.

Lingle

WL

,

Barrett

SL

,

Negron

VC

, et al.

Centrosome amplification drives chromosomal instability in breast tumor development

.

Proc Natl Acad Sci U S A

.

2002

;

99

(

4

):

1978

-

1983

.

11.

Tian

X

,

Zhou

D

,

Chen

L

, et al.

Polo-like kinase 4 mediates epithelial-mesenchymal transition in neuroblastoma via PI3K/Akt signaling pathway

.

Cell Death Dis

.

2018

;

9

(

2

):

54

.

12.

Zhang

Z

,

Wang

Z

,

Huang

K

, et al.

PLK4 is a determinant of temozolomide sensitivity through phosphorylation of IKBKE in glioblastoma

.

Cancer Lett

.

2019

;

443

:

91

-

107

.

13.

Bao

J

,

Yu

Y

,

Chen

J

, et al.

MiR-126 negatively regulates PLK-4 to impact the development of hepatocellular carcinoma via ATR/CHEK1 pathway

.

Cell Death Dis

.

2018

;

9

(

10

):

1045

.

14.

Li

J

,

Tan

M

,

Li

L

,

Pamarthy

D

,

Lawrence

TS

,

Sun

Y

.

SAK, a new polo-like kinase, is transcriptionally repressed by p53 and induces apoptosis upon RNAi silencing

.

Neoplasia

.

2005

;

7

(

4

):

312

-

323

.

15.

Ward

A

,

Hudson

JW

.

p53-Dependent and cell specific epigenetic regulation of the polo-like kinases under oxidative stress

.

PLoS One

.

2014

;

9

(

1

):

e87918

.

16.

Serçin

Ö

,

Larsimont

JC

,

Karambelas

AE

, et al.

Transient PLK4 overexpression accelerates tumorigenesis in p53-deficient epidermis

.

Nat Cell Biol

.

2016

;

18

(

1

):

100

-

110

.

17.

Meek

DW

.

The role of p53 in the response to mitotic spindle damage

.

Pathol Biol (Paris)

.

2000

;

48

(

3

):

246

-

254

.

18.

Webster

ALH

,

Sanders

MA

,

Patel

K

, et al.

Genomic signature of Fanconi anaemia DNA repair pathway deficiency in cancer

.

Nature

.

2022

;

612

(

7940

):

495

-

502

.

19.

Frankish

A

,

Diekhans

M

,

Jungreis

I

, et al.

GENCODE 2021

.

Nucleic Acids Res

.

2021

;

49

(

D1

):

D916

-

d923

.

20.

Wu

T

,

Liu

W

,

Huang

S

, et al.

clusterProfiler 4.0: A universal enrichment tool for interpreting omics data

.

Innovation (Camb)

.

2021

;

12

(

3

):

100141

.

21.

Man

CH

,

Mercier

FE

,

Liu

N

, et al.

Proton export alkalinizes intracellular pH and reprograms carbon metabolism to drive normal and malignant cell growth

.

Blood

.

2022

;

139

(

4

):

502

-

522

.

22.

Zhao

Y

,

Yang

J

,

Liu

J

, et al.

Inhibition of Polo-like kinase 4 induces mitotic defects and DNA damage in diffuse large B-cell lymphoma

.

Cell Death Dis

.

2021

;

12

(

7

):

640

.

23.

Kojima

K

,

Konopleva

M

,

Samudio

IJ

, et al.

MDM2 antagonists induce p53-dependent apoptosis in AML: implications for leukemia therapy

.

Blood

.

2005

;

106

(

9

):

3150

-

3159

.

24.

Liu

F

,

Xu

Y

,

Lu

X

, et al.

PRMT5-mediated histone arginine methylation antagonizes transcriptional repression by polycomb complex PRC2

.

Nucleic Acids Res

.

2020

;

48

(

6

):

2956

-

2968

.

25.

Li

Z

,

Xu

J

,

Song

Y

, et al.

PRMT5 Prevents dilated cardiomyopathy via suppression of protein O-GlcNAcylation

.

Circ Res

.

2021

;

129

(

9

):

857

-

871

.

26.

Chu

CS

,

Lo

PW

,

Yeh

YH

, et al.

O-GlcNAcylation regulates EZH2 protein stability and function

.

Proc Natl Acad Sci U S A

.

2014

;

111

(

4

):

1355

-

1360

.

27.

Aarreberg

LD

,

Esser-Nobis

K

,

Driscoll

C

,

Shuvarikov

A

,

Roby

JA

,

Gale

M

.

Interleukin-1beta induces mtDNA release to activate innate immune signaling via cGAS-STING

.

Mol Cell

.

2019

;

74

(

4

):

801

-

815.e6

.

28.

Chan

CY

,

Yuen

VW

,

Chiu

DK

, et al.

Polo-like kinase 4 inhibitor CFI-400945 suppresses liver cancer through cell cycle perturbation and eliciting antitumor immunity

.

Hepatology

.

2023

;

77

(

3

):

729

-

744

.

29.

Li

T

,

Chen

ZJ

.

The cGAS-cGAMP-STING pathway connects DNA damage to inflammation, senescence, and cancer

.

J Exp Med

.

2018

;

215

(

5

):

1287

-

1299

.

30.

Dou

Z

,

Ghosh

K

,

Vizioli

MG

, et al.

Cytoplasmic chromatin triggers inflammation in senescence and cancer

.

Nature

.

2017

;

550

(

7676

):

402

-

406

.

31.

Gu

X

,

Guan

J

,

Xu

J

, et al.

Model based on five tumour immune microenvironment-related genes for predicting hepatocellular carcinoma immunotherapy outcomes

.

J Transl Med

.

2021

;

19

(

1

):

26

.

32.

Jiang

Y

,

Ji

Q

,

Long

X

, et al.

CLCF1 Is a novel potential immune-related target with predictive value for prognosis and immunotherapy response in glioma

.

Front Immunol

.

2022

;

13

:

810832

.

33.

Tamura

M

,

Yonezawa

T

,

Liu

X

, et al.

Opposing effects of acute versus chronic inhibition of p53 on decitabine's efficacy in myeloid neoplasms

.

Sci Rep

.

2019

;

9

(

1

):

8171

.

34.

Kawakami

M

,

Mustachio

LM

,

Zheng

L

, et al.

Polo-like kinase 4 inhibition produces polyploidy and apoptotic death of lung cancers

.

Proc Natl Acad Sci U S A

.

2018

;

115

(

8

):

1913

-

1918

.

35.

Singh

CK

,

Denu

RA

,

Nihal

M

, et al.

PLK4 is upregulated in prostate cancer and its inhibition reduces centrosome amplification and causes senescence

.

Prostate

.

2022

;

82

(

9

):

957

-

969

.

36.

Deng

S

,

Lu

X

,

Zhang

Z

,

Meng

R

,

Li

M

,

Xia

S

.

Identification and assessment of PLK1/2/3/4 in lung adenocarcinoma and lung squamous cell carcinoma: Evidence from methylation profile

.

J Cell Mol Med

.

2021

;

25

(

14

):

6652

-

6663

.

37.

Oegema

K

,

Davis

RL

,

Lara-Gonzalez

P

,

Desai

A

,

Shiau

AK

.

CFI-400945 is not a selective cellular PLK4 inhibitor

.

Proc Natl Acad Sci U S A

.

2018

;

115

(

46

):

E10808

-

e10809

.

38.

Sampson

PB

,

Liu

Y

,

Forrest

B

, et al.

The discovery of Polo-like kinase 4 inhibitors: identification of (1R,2S).2-(3-((E).4-(((cis).2,6-dimethylmorpholino)methyl)styryl). 1H.indazol-6-yl)-5'-methoxyspiro[cyclopropane-1,3'-indolin]-2'-one (CFI-400945) as a potent, orally active antitumor agent

.

J Med Chem

.

2015

;

58

(

1

):

147

-

169

.

39.

Massett

ME

,

Monaghan

L

,

Patterson

S

, et al.

A KDM4A-PAF1-mediated epigenomic network is essential for acute myeloid leukemia cell self-renewal and survival

.

Cell Death Dis

.

2021

;

12

(

6

):

573

.

40.

Yang

L

,

Ma

DW

,

Cao

YP

, et al.

PRMT5 functionally associates with EZH2 to promote colorectal cancer progression through epigenetically repressing CDKN2B expression

.

Theranostics

.

2021

;

11

(

8

):

3742

-

3759

.

41.

Gollner

S

,

Oellerich

T

,

Agrawal-Singh

S

, et al.

Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia

.

Nat Med

.

2017

;

23

(

1

):

69

-

78

.

42.

Rath

BH

,

Waung

I

,

Camphausen

K

,

Tofilon

PJ

.

Inhibition of the histone H3K27 demethylase UTX enhances tumor cell radiosensitivity

.

Mol Cancer Ther

.

2018

;

17

(

5

):

1070

-

1078

.

43.

Zeidler

M

,

Varambally

S

,

Cao

Q

, et al.

The polycomb group protein EZH2 impairs DNA repair in breast epithelial cells

.

Neoplasia

.

2005

;

7

(

11

):

1011

-

1019

.

44.

Li

Y

,

Zhang

M

,

Sheng

M

, et al.

Therapeutic potential of GSK-J4, a histone demethylase KDM6B/JMJD3 inhibitor, for acute myeloid leukemia

.

J Cancer Res Clin Oncol

.

2018

;

144

(

6

):

1065

-

1077

.

45.

Ma

D

,

Yang

M

,

Wang

Q

, et al.

Arginine methyltransferase PRMT5 negatively regulates cGAS-mediated antiviral immune response

.

Sci Adv

.

2021

;

7

(

13

):

eabc1834

.

46.

Kim

H

,

Kim

H

,

Feng

Y

, et al.

PRMT5 control of cGAS/STING and NLRC5 pathways defines melanoma response to antitumor immunity

.

Sci Transl Med

.

2020

;

12

(

551

):

eaaz5683

.

47.

Lehmann

BD

,

Paine

MS

,

Brooks

AM

, et al.

Senescence-associated exosome release from human prostate cancer cells

.

Cancer Res

.

2008

;

68

(

19

):

7864

-

7871

.

48.

Yokoi

A

,

Villar-Prados

A

,

Oliphint

PA

, et al.

Mechanisms of nuclear content loading to exosomes

.

Sci Adv

.

2019

;

5

(

11

):

eaax8849

.

49.

Han

C

,

Godfrey

V

,

Liu

Z

, et al.

The AIM2 and NLRP3 inflammasomes trigger IL-1-mediated antitumor effects during radiation

.

Sci Immunol

.

2021

;

6

(

59

):

eabc6998

.

50.

Bromley

SK

,

Mempel

TR

,

Luster

AD

.

Orchestrating the orchestrators: chemokines in control of T cell traffic

.

Nat Immunol

.

2008

;

9

(

9

):

970

-

980

.

51.

Yoshimura

T

.

The chemokine MCP-1 (CCL2) in the host interaction with cancer: a foe or ally?

.

Cell Mol Immunol

.

2018

;

15

(

4

):

335

-

345

.

52.

Jin

J

,

Lin

J

,

Xu

A

, et al.

CCL2: An important mediator between tumor cells and host cells in tumor microenvironment

.

Front Oncol

.

2021

;

11

:

722916

.

53.

Dehmani

S

,

Nerrière-Daguin

V

,

Néel

M

, et al.

SIRPγ-CD47 interaction positively regulates the activation of human T cells in situation of chronic stimulation

.

Front Immunol

.

2021

;

12

:

732530

.

54.

Daver

NG

,

Vyas

P

,

Kambhampati

S

, et al.

Tolerability and efficacy of the first-in-class anti-CD47 antibody magrolimab combined with azacitidine in frontline TP53m AML patients: Phase 1b results

.

J Clin Oncol

.

2022

;

40

(

16_suppl

):

7020

.