Hallmarks of Cancer: New Dimensions
Cancer Discovery,
Год журнала:
2022,
Номер
12(1), С. 31 - 46
Опубликована: Янв. 1, 2022
The
hallmarks
of
cancer
conceptualization
is
a
heuristic
tool
for
distilling
the
vast
complexity
phenotypes
and
genotypes
into
provisional
set
underlying
principles.
As
knowledge
mechanisms
has
progressed,
other
facets
disease
have
emerged
as
potential
refinements.
Herein,
prospect
raised
that
phenotypic
plasticity
disrupted
differentiation
discrete
hallmark
capability,
nonmutational
epigenetic
reprogramming
polymorphic
microbiomes
both
constitute
distinctive
enabling
characteristics
facilitate
acquisition
capabilities.
Additionally,
senescent
cells,
varying
origins,
may
be
added
to
roster
functionally
important
cell
types
in
tumor
microenvironment.
SIGNIFICANCE:
Cancer
daunting
breadth
scope
its
diversity,
spanning
genetics,
tissue
biology,
pathology,
response
therapy.
Ever
more
powerful
experimental
computational
tools
technologies
are
providing
an
avalanche
"big
data"
about
myriad
manifestations
diseases
encompasses.
integrative
concept
embodied
helping
distill
this
increasingly
logical
science,
new
dimensions
presented
perspective
add
value
endeavor,
fully
understand
development
malignant
progression,
apply
medicine.
Язык: Английский
The molecular hallmarks of epigenetic control
Nature Reviews Genetics,
Год журнала:
2016,
Номер
17(8), С. 487 - 500
Опубликована: Июнь 27, 2016
Язык: Английский
The diverse roles of DNA methylation in mammalian development and disease
Nature Reviews Molecular Cell Biology,
Год журнала:
2019,
Номер
20(10), С. 590 - 607
Опубликована: Авг. 9, 2019
Язык: Английский
Dynamics and function of DNA methylation in plants
Nature Reviews Molecular Cell Biology,
Год журнала:
2018,
Номер
19(8), С. 489 - 506
Опубликована: Май 21, 2018
Язык: Английский
DNA Methylation in Mammals
Cold Spring Harbor Perspectives in Biology,
Год журнала:
2014,
Номер
6(5), С. a019133 - a019133
Опубликована: Май 1, 2014
En
Li1
and
Yi
Zhang2
1China
Novartis
Institutes
for
BioMedical
Research,
Pudong
New
Area,
Shanghai
201203,
China
2Boston
Children's
Hospital,
Harvard
Medical
School,
Boston,
Massachusetts
02115
Correspondence:
en.li{at}novartis.com
Язык: Английский
Histone Modifications and Cancer
Cold Spring Harbor Perspectives in Biology,
Год журнала:
2016,
Номер
8(4), С. a019521 - a019521
Опубликована: Апрель 1, 2016
Histone
posttranslational
modifications
represent
a
versatile
set
of
epigenetic
marks
involved
not
only
in
dynamic
cellular
processes,
such
as
transcription
and
DNA
repair,
but
also
the
stable
maintenance
repressive
chromatin.
In
this
article,
we
review
many
key
newly
identified
histone
known
to
be
deregulated
cancer
how
impacts
function.
The
latter
part
article
addresses
challenges
current
status
drug
development
process
it
applies
therapeutics.
Язык: Английский
Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma
Nature Materials,
Год журнала:
2017,
Номер
16(11), С. 1155 - 1161
Опубликована: Окт. 9, 2017
Язык: Английский
Genomic Imprinting in Mammals
Cold Spring Harbor Perspectives in Biology,
Год журнала:
2014,
Номер
6(2), С. a018382 - a018382
Опубликована: Фев. 1, 2014
Denise
P.
Barlow1
and
Marisa
S.
Bartolomei2
1CeMM
Research
Center
for
Molecular
Medicine
of
the
Austrian
Academy
Sciences,
CeMM,
1090
Vienna,
Austria
2Department
Cell
Developmental
Biology,
University
Pennsylvania
Perelman
School
Medicine,
Philadelphia,
19104-6148
Correspondence:
dbarlow{at}cemm.oeaw.ac.at
bartolom{at}mail.med.upenn.edu
Язык: Английский
Navigating the DNA methylation landscape of cancer
Trends in Genetics,
Год журнала:
2021,
Номер
37(11), С. 1012 - 1027
Опубликована: Июнь 10, 2021
DNA
methylation
is
an
important
epigenetic
modification
that
defines
the
properties
of
cells.
Genome-wide
hypomethylation,
as
well
hypermethylation
CpG
islands
associated
with
tumor
suppressor
genes
and
developmental
regulators,
are
characteristics
cancer
cells.DNA
methyltransferases
normally
exist
in
inactive
form
their
localization
activation
regulated
by
interaction
unique
histone
modifications
at
sites.Changes
patterns
carcinogenesis
progress
gradually
cell
proliferation.
hypomethylation
found
blocks
called
partially
methylated
domains
(PMDs)
it
frequently
occurs
solo-WCGW
sequences
have
no
nearby
adjacent
to
A
or
C.CpG
island
primarily
targets
promoters
characterized
low
gene
expression
marked
H3K27m3,
replacement
ensuring
more
stable
repression.
a
chemical
type
lineage
through
control
genome
stability.
Disruption
mechanisms
causes
variety
diseases,
including
cancer.
Cancer
cells
aberrant
(i.e.,
genome-wide
site-specific
hypermethylation),
mainly
targeting
regulatory
elements.
In
particular,
early
findings
(TSGs)
led
proposal
model
which
promotes
cellular
oncogenesis
TSGs
silencing.
However,
recent
analyses
revealed
this
classical
needs
be
reconsidered.
review,
we
will
discuss
molecular
abnormalities
therapeutic
potential.
plays
role
regulation
[1.Yisraeli
J.
et
al.Muscle-specific
chimeric
actin
gene.Cell.
1986;
46:
409-416Abstract
Full
Text
PDF
PubMed
Scopus
(0)
Google
Scholar,
2.Busslinger
M.
al.DNA
globin
expression.Cell.
1983;
34:
197-206Abstract
3.Siegfried
Z.
represses
transcription
vivo.Nat.
Genet.
1999;
22:
203-206Crossref
(268)
Scholar],
genomic
imprinting
[4.Li
E.
al.Role
for
imprinting.Nature.
1993;
366:
362-365Crossref
(1684)
5.Stöger
R.
al.Maternal-specific
imprinted
mouse
Igf2r
locus
identifies
expressed
carrying
signal.Cell.
73:
61-71Abstract
6.Ferguson-Smith
A.C.
al.Parental-origin-specific
H19
gene.Nature.
362:
751-755Crossref
X
chromosome
inactivation
[7.Mohandas
T.
al.Reactivation
human
chromosome:
evidence
methylation.Science.
1981;
211:
393-396Crossref
Scholar,8.Wolf
S.F.
al.Methylation
hypoxanthine
phosphoribosyltransferase
on
implications
X-chromosome
inactivation.Proc.
Natl.
Acad.
Sci.
U.
S.
A.
1984;
81:
2806-2810Crossref
transposon
(see
Glossary)
silencing
[9.Walsh
C.P.
al.Transcription
IAP
endogenous
retroviruses
constrained
cytosine
methylation.Nat.
1998;
20:
116-117Crossref
(808)
stability
[10.Eden
al.Chromosomal
instability
tumors
promoted
hypomethylation.Science.
2003;
300:
455Crossref
(1008)
Scholar,11.Karpf
A.R.
Matsui
Genetic
disruption
methyltransferase
enzymes
induces
chromosomal
cells.Cancer
Res.
2005;
65:
8635-8639Crossref
(190)
Scholar].
catalyzed
three
enzymes,
DNMT1,
DNMT3A,
DNMT3B
(Figure
1).
De
novo
(DNMTs)
DNMT3A
3B
(Box
1),
while
established
maintained
daughter
maintenance
mechanism
during
proliferation
2).
Both
de
normal
development.
DNMT1
DNMT3A/3B
double
knockout
(KO)
embryos
show
significant
growth
inhibition
lethal
before
mid-gestation
[12.Li
al.Targeted
mutation
results
embryonic
lethality.Cell.
1992;
69:
915-926Abstract
(3073)
Scholar,13.Okano
Dnmt3a
Dnmt3b
essential
mammalian
development.Cell.
99:
247-257Abstract
(4122)
contrast,
not
necessarily
required
stem
(ES)
cells;
even
when
completely
lost
combined
KO
DNMTs
Dnmt1,
Dnmt3a,
Dnmt3b,
there
minimal
change
phenotype
undifferentiated
ES
[14.Tsumura
al.Maintenance
self-renewal
ability
absence
Dnmt3b.Genes
Cells.
2006;
11:
805-814Crossref
(380)
Although
modification,
also
several
pathways
demethylation
these
play
various
biological
contexts
3).
cells,
most
methylated,
but
shores
(the
region
within
2
kb
islands)
exceptionally
hypomethylated
[15.Irizarry
R.A.
al.The
colon
methylome
shows
similar
hypo-
conserved
tissue-specific
shores.Nat.
2009;
41:
178-186Crossref
(1528)
Scholar,16.Doi
al.Differential
tissue-
cancer-specific
distinguishes
induced
pluripotent
fibroblasts.Nat.
1350-1353Crossref
(892)
Many
regions
function
elements
regulate
expression,
such
enhancers.
addition,
systematic
analysis
unmethylated
ligands
has
binding
many
factors
[17.Yin
Y.
al.Impact
specificities
factors.Science.
2017;
356eaaj2239Crossref
(373)
Recently,
broad
were
reported
canyons
[18.Jeong
al.Large
Dnmt3a.Nat.
2014;
17-23Crossref
(203)
Scholar]
valleys
[19.Xie
W.
al.Epigenomic
multilineage
differentiation
cells.Cell.
2013;
153:
1134-1148Abstract
(475)
either
active
mark
H3K4me3
inhibitory
H3K27me3.Figure
2Regulatory
activity
localization.Show
full
caption(A)
H3,
exists
autoinhibitory
state,
ATRX-DNMT3A-DNMT3L
(ADD)
domain
interacts
catalytic
(CD)
inhibit
binding.
H3K4me0
ADD
break
autoinhibition
activate
DNMT3A.
release
H3K36me3
Pro-Trp-Trp-Pro
(PWWP)
promote
body.
It
been
H3K36Kme2
similarly
regulates
intergenic
PWWP
domain.
(B)
DNMT3A2
DNMT3B3,
catalytically
subunits,
heterotetrameric
3B3-3A2-3A2-3B3.
One
two
catalytic-like
DNMT3B3
acidic
patch
nucleosome
core
particle,
leading
linker
DNA.
The
chromatin
(DNMT)
complexes
methylation,
indicating
importance
patch,
addition
H3K36me2
me3.View
Large
Image
Figure
ViewerDownload
Hi-res
image
Download
(PPT)Box
1De
methylationMammalian
sites
methyltransferases,
[13.Okano
Scholar,125.Okano
al.Cloning
characterization
family
novel
(cytosine-5)
methyltransferases.Nat.
19:
219-220Crossref
(1206)
DNMT3
proteins
composed
N
terminal
region,
central
enzyme
C
1)
[126.Goll
M.G.
Bestor
T.H.
Eukaryotic
methyltransferases.Annu.
Rev.
Biochem.
74:
481-514Crossref
(1492)
roles
target
enzymatic
activity.
proper
[127.Ge
Y.-Z.
al.Chromatin
domain.J.
Biol.
Chem.
2004;
279:
25447-25454Abstract
(148)
acts
reader
module
recognize
bind
histones
[128.Dhayalan
reads
3
lysine
36
trimethylation
guides
methylation.J.
2010;
285:
26114-26120Abstract
(330)
Histone
enriches
body
actively
transcribed
undergoing
catalysis
SETD2
protein
(also
RNAPII
subunit
B1),
binds
RNA
polymerase
II
[129.Wagner
E.J.
Carpenter
P.B.
Understanding
language
Lys36
H3.Nat.
Mol.
Cell
2012;
13:
115-126Crossref
(534)
130.Kizer
K.O.
al.A
Set2
mediates
couples
H3
K36
transcript
elongation.Mol.
Cell.
25:
3305-3316Crossref
(329)
131.Krogan
N.J.
Saccharomyces
cerevisiae
linked
transcriptional
elongation
II.Mol.
23:
4207-4218Crossref
(492)
[132.Baubec
al.Genomic
profiling
reveals
genic
methylation.Nature.
2015;
520:
243-247Crossref
(350)
Transcription-
H3K36me3-mediated
establishment
oocyte
[133.Xu
Q.
al.SETD2
maternal
epigenome,
development.Nat.
2019;
51:
844-856Crossref
(64)
Several
studies
shown
differently.
NSD1
NSD2
K36me2
using
mesenchymal
(MSCs)
showed
depends
MSCs
[134.Weinberg
D.N.
recruits
shapes
landscape.Nature.
573:
281-286Crossref
(97)
NSD1-mediated
recently
male
germlines
[135.Shirane
K.
al.NSD1-deposited
directs
germline
counteracts
Polycomb-associated
silencing.Nat.
2020;
52:
1088-1098Crossref
(15)
Thus,
H3K36me2-enriched
H3K36me3-enriched
bodies
may
specify
DNMT3B,
respectively,
domain.The
recognizes
unmodified
4
[136.Ooi
S.K.
al.DNMT3L
connects
DNA.Nature.
2007;
448:
714-717Crossref
(1040)
crystal
structure
complex
amino-terminal
tail
specific
H3K4me0,
H3K4me2
[137.Otani
al.Structural
basis
recognition
H3K4
status
3A
ATRX–DNMT3–DNMT3L
domain.EMBO
Rep.
10:
1235-1241Crossref
(250)
138.Guo
X.
insight
into
H3-induced
DNMT3A.Nature.
517:
640-644Crossref
(188)
139.Noh
K.-M.
al.Engineering
histone-recognition
alters
landscape
phenotypic
features
ESCs.Mol.
59:
89-103Abstract
These
consistent
fact
distribution
mutually
exclusive
[138.Guo
140.Zhang
Dnmt3a/3L
guided
tail.Nucleic
Acids
38:
4246-4253Crossref
(243)
141.Li
B.-Z.
al.Histone
tails
allosterically
activating
methyltransferase.Cell
2011;
21:
1172-1181Crossref
(81)
142.Guibert
al.Global
erasure
primordial
germ
cells.Genome
633-641Crossref
(224)
Moreover,
stimulates
vitro
Scholar,140.Zhang
Scholar,141.Li
tail,
directly
inhibits
(CD).
H3K4me3,
disrupts
ADD-CD
cancels
2A)
This
would
ensure
suppression
unfavorable
H3K4me3-marked
promoter,
recruited.Figure
3Ubiquitin-like,
containing
PHD
RING
finger
1
(UHRF1)-dependent
ubiquitin
signaling
orchestrates
methylation.Show
captionDuring
replication,
converted
hemi-methylated
only
parent
strand
methylated.
UHRF1
specifically
Lys
residues
terminus
PCNA-associated
factor
15
(PAF15)
dual
monoubiquitylation.
Ubiquitinated
PAF15
RFTS
DNMT1.
Hemi-methylated
left
after
passage
replication
machinery
fully
DNA,
probably
via
UHRF1-dependent
monoubiquitination
H3.
between
USP7
indicates
act
deubiquitinating
antagonizes
UHRF1.View
2Maintenance
methylationProper
require
factors.
Early
demonstrated
colocalizes
PCNA
foci
[143.Chuang
L.
al.Human
DNA-(cytosine-5)
methyltransferase-PCNA
p21WAF1.Science.
1997;
277:
1996-2000Crossref
(755)
later
was
DNMT1/PCNA
[144.Spada
F.
al.DNMT1
its
cells.J.
176:
565-571Crossref
(145)
Scholar,145.Easwaran
H.P.
al.Replication-independent
loading
Dnmt1
G2
M
phases.EMBO
5:
1181-1186Crossref
(130)
Ubiquitin-like,
(UHRF1),
ICPB90
humans
Np95
mice,
critical
[116.Sharif
SRA
inheritance
recruiting
450:
908-912Crossref
(830)
Scholar,117.Bostick
al.UHRF1
Plays
maintaining
cells.Science.
317:
1760-1764Crossref
(867)
SET-
RING-associated
(SRA)
[146.Arita
al.Recognition
base-flipping
mechanism.Nature.
2008;
455:
818-821Crossref
(335)
147.Hashimoto
H.
flips
5-methylcytosine
out
helix.Nature.
826-829Crossref
(300)
148.Avvakumov
G.V.
UHRF1.Nature.
822-825Crossref
(331)
accumulates
recruit
Recent
indicated
E3
ligase
efficient
methylation.
Upon
SRA-mediated
mono-ubiquitylates
Lys14-,
Lys18,
and/or
23
[115.Nishiyama
al.Uhrf1-dependent
H3K23
ubiquitylation
replication.Nature.
502:
249-253Crossref
(206)
Scholar,149.Ishiyama
al.Structure
complexed
two-mono-ubiquitin
maintenance.Mol.
68:
350-360Abstract
Scholar,150.Qin
requires
interacting
motif
(UIM)
ubiquitination.Cell
911-929Crossref
(127)
Hemi-methyl-DNA
accessibility
[120.Harrison
J.S.
al.Hemi-methylated
allosteric
UHRF1.eLife.
2016;
5e17101Crossref
Scholar,151.Fang
opens
closed
conformation
facilitate
recognition.Nat.
Commun.
7:
11197Crossref
(66)
Ubiquitin-like
(UBL)
contributes
E2
ubiquitin-conjugating
Ubch5a/UBE2D1
[123.Foster
B.M.
al.Critical
UBL
stimulating
toward
chromatin.Mol.
2018;
72:
739-752Abstract
(31)
Scholar,124.DaRosa
P.A.
bifunctional
DNA-dependent
ubiquitylation.Mol.
753-765Abstract
(29)
Multiple
mono-ubiquitylated
turn
recognized
bound
modules
DNMT1-RFTS
[118.Li
mechanistic
insights
UHRF1-mediated
methylation.Nucleic
3218-3231Crossref
(53)
previously
recruitment
[152.Leonhardt
sequence
nuclei.Cell.
71:
865-873Abstract
(784)
proposed
pocket
[153.Takeshita
(Dnmt1).Proc.
108:
9055-9059Crossref
Scholar,154.Syeda
focus
(RFTS)
DNA-competitive
inhibitor
Dnmt1.J.
286:
15344-15351Abstract
(76)
Importantly,
enhances
[149.Ishiyama
presumably
gross
conformational
opening
site.
data
indicate
ubiquitylated
platform
DNMT1.Recently,
emerged
another
substrate
multiple
mono-ubiquitylation
[121.Nishiyama
al.Two
distinct
modes
1222Crossref
(25)
Scholar,155.Karg
al.Ubiquitome
ubiquitination
429:
3814-3824Crossref
(19)
2VRTK5,
extreme
PAF15,
manner
ARTK
suggesting
recognizing
end
proteins.
During
S
phase,
undergoes
evolutionarily
replication-coupled
front
face
inner
ring
exits
clamp
from
back
[156.March
al.p15PAF
modulates
sliding
surface.Nucleic
9816-9828Crossref
(7)
could
PCNA,
facilitating
3).Box
3DNA
demethylationDuring
development,
pattern
fluctuates
dynamically
[142.Guibert
Scholar,157.Hajkova
P.
dynamics
reprogramming
line.Nature.
452:
877-881Crossref
(482)
Scholar,158.Hackett
J.A.
al.Germline
imprint
5-hydroxymethylcytosine.Science.
339:
448-452Crossref
(511)
particularly
preimplantation
(PGC)
setting
up
states
erasing
parental-origin-specific
imprints
developing
PGCs
[159.Lee
al.Erasing
memory
clone
produced
day
11.5
cells.Development.
2002;
129:
1807-1817Crossref
(50)
Scholar,160.Hill
demethylation,
Tet
5-hydroxymethylcytosine
reprogramming:
emerging
story.Genomics.
104:
324-333Crossref
(101)
different
pathways:
(i)
replication-dependent
dilution
marks
[161.Kagiwada
al.Replication-coupled
passive
mice.EMBO
32:
340-353Crossref
(197)
162.Ohno
140:
2892-2903Crossref
(52)
163.Seisenberger
cells.Mol.
48:
849-862Abstract
(575)
164.Kurimoto
al.Complex
orchestrated
Blimp1
specification
mice.Gene
Dev.
1617-1635Crossref
(ii)
Ten-eleven
Translocation
(TET)-dependent
[165.Yamaguchi
Tet1
504:
460-464Crossref
166.Yamaguchi
al.Tet1
controls
meiosis
regulating
meiotic
expression.Nature.
492:
443-447Crossref
(182)
167.Wu
Zhang
Reversing
methylati
Язык: Английский
Circular ecDNA promotes accessible chromatin and high oncogene expression
Nature,
Год журнала:
2019,
Номер
575(7784), С. 699 - 703
Опубликована: Ноя. 20, 2019
Язык: Английский
