Investigation of aberrant WNT signaling in colorectal cancer cells:
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| 1. Verfasser: | |
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| Format: | Abschlussarbeit Buch |
| Sprache: | English |
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Heidelberg
2019
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| Beschreibung: | 218 Seiten Illustrationen, Diagramme |
Internformat
MARC
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| 008 | 201008s2019 gw a||| m||| 00||| eng d | ||
| 016 | 7 | |a 1217737995 |2 DE-101 | |
| 020 | |c Broschur | ||
| 035 | |a (OCoLC)1196228946 | ||
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| 100 | 1 | |a Ambrosi, Giulia |d 1988- |e Verfasser |0 (DE-588)1189461374 |4 aut | |
| 245 | 1 | 0 | |a Investigation of aberrant WNT signaling in colorectal cancer cells |c Giulia Ambrosi |
| 264 | 1 | |a Heidelberg |c 2019 | |
| 300 | |a 218 Seiten |b Illustrationen, Diagramme | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |b Dissertation |c Ruperto-Carola University of Heidelberg, Germany |d 2019 | ||
| 655 | 7 | |0 (DE-588)4113937-9 |a Hochschulschrift |2 gnd-content | |
| 856 | 4 | 2 | |m B:DE-101 |q application/pdf |u https://d-nb.info/1217737995/04 |3 Inhaltsverzeichnis |
| 856 | 4 | 2 | |m DNB Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=032339956&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-032339956 | ||
Datensatz im Suchindex
| _version_ | 1804181825677950976 |
|---|---|
| adam_text | TABLE
OF
CONTENT
LIST
OF
FIGURES
....................................................................................................................
3
LIST
OF
TABLES
......................................................................................................................
5
ABBREVIATIONS
.....................................................................................................................
7
ABSTRACT
...............................................................................................................................
8
ZUSAMMENFASSUNG
............................................................................................................
9
ACKNOWLEDGMENTS
...........................................................................................................
11
1
INTRODUCTION
..........................................................................................................
14
1.1
R
EGULATION
OF
SIGNAL
TRANSDUCTION
PATHWAYS
.......................................................
14
1.1.1
LIQUID-LIQUID
PHASE
SEPARATION
TUNES
SIGNAL
TRANSDUCTION
....................................
14
1.2
W
NT
SIGNALING
PATHWAY
..............................................................................................
15
1.2.1
THE
WNT/B-CATENIN
SIGNALING
PATHWAY
..................................................................
17
1.2.2
DUAL
ROLE
OF
B-CATENIN
PROTEIN
IN
SIGNAL
TRANSDUCTION
AND
ADHESION
....................
21
1.2.3
WNT
SIGNALING
AND
COLORECTAL
CANCER
CARCINOGENESIS
........................................28
1.2.4
TARGETED
THERAPY
OF
THE
WNT
SIGNALING
PATHWAY
.................................................
32
1.3
N
OVEL
METHODS
TO
INVESTIGATE
SIGNALING
PATHWAYS
...............................................
35
1.3.1
RECOMBINANT
DNA
TECHNOLOGY:
GENOME
EDITING
NUCLEASES
................................
35
2
AIMS
OF
THIS
STUDY
................................................................................................
44
3
RESULTS
.....................................................................................................................46
3.1
I
N
VITRO
MODEL
OF
ARC
LOSS
OF
FUNCTION
COLORECTAL
CANCER
CELLS
.................
46
3.1.1
ARC
IS
A
MULTIFUNCTIONAL
SCAFFOLD
PROTEIN
.............................................................
46
3.1.2
RKO
AND
HCT116
CELL
LINES
AS
SUITABLE
IN
VITRO
MODEL
OF
APC
LOF
......................
49
3.1.3
GENERATION
AND
VALIDATION
OF
RKO
ISOGENIC
CELL
LINES
WITH
APC
L0F
MUTATIONS....
54
3.1.4
GENERATION
AND
VALIDATION
OF
HCT116
ISOGENIC
CELL
LINES
WITH
APC
LOF
MUTATIONS
57
3.1.5
APC
LOF
MUTATIONS
CHANGE
CELLULAR
MORPHOLOGY
...................................................
58
3.2
MEK
INHIBITION
ACTIVATES
WNT
SIGNALING
IN
ORO
CELLS
.........................................
63
3.2.1
RAS-ERK
AND
WNT
SIGNALING
MUTATIONS
IN
COLORECTAL
CANCER
...........................
63
3.2.2
SMALL
COMPOUND
CLASS
OF
MEK
INHIBITORS
AS
ACTIVATORS
OF
WNT/B-CATENIN
SIGNALING
65
3.2.3
TRAMETINIB
SYNERGIZES
WITH
CTNNB1
AND
APC
LOF
MUTATIONS
IN
THE
INDUCTION
OF
WNT
SIGNALING
............................................................................................................................
67
3.2.4
MEK
INHIBITOR
INDUCES
A
DECREASE
OF
AXINL
STABILITY
...........................................70
3.2.5
AXINL
E3
UBIQUITIN
LIGASES
ARE
NOT
INVOLVED
IN
WNT
SIGNALING
ACTIVATION
UPON
MEK
INHIBITION
............................................................................................................................
73
3.2.6
TRANSCRIPTIONAL
REGULATION
OF
AXINL
BY
EGR1
.......................................................74
3.2.7
MEK
INHIBITION
IMPAIRS
THE
FORMATION
OF
AN
INTACT
AXINL
COMPLEX
.......................75
3.2.8
SYNERGISM
BETWEEN
MEK
AND
WNT
INHIBITION
IN
REPRESSING
CRC
TUMOR
GROWTH
77
3.3
E
NDOGENOUS
S
-
CATENIN
PROTEIN
TAGGING
..................................................................80
3.3.1
ENDOGENOUS
PROTEIN
TAGGING
USING
CRISPR-CAS9
TECHNOLOGY
..........................80
3.3.2
STRATEGY
DESIGN
OF
B-CATENIN
PROTEIN
TAGGING
.......................................................84
3.3.3
EVALUATION
OF
KNOCK-IN
EFFICIENCY
AT
THE
B-CATENIN
LOCUS
......................................87
3.3.4
SELECTION
AND
CHARACTERIZATION
OF
CTNNB1
KI
CELLS
..............................................
91
3.3.5
FUNCTIONAL
CHARACTERIZATION
OF
ENDOGENOUSLY
TAGGED
B-CATENIN
CELL
LINES
..........97
3.3.6
WILD-TYPE
AND
MUTANT
B-CATENIN
BELONGS
TO
TWO
DIFFERENT
POOLS
IN
THE
CELLS
.......
106
3.3.7
CHARACTERIZATION
OF
B-CATENIN
SPATIAL
DYNAMICS
IN
LIVE
CELLS
USING
FLUORESCENCE
CORRELATION
SPECTROSCOPY
(FCS)
...............................................................................................
111
3.4
T
OWARDS
IDENTIFICATION
OF
ARC
LOSS
OF
FUNCTION
VULNERABILITIES
....................
123
3.4.1
CRISPR/CAS9
FUNCTIONAL
GENETIC
SCREENS
..........................................................
123
3.4.2
GENOME-WIDE
CRISPR/CAS9
SCREEN
IN
ISOGENIC
CRC
CELLS
.............................
125
3.4.3
GENOME-WIDE
CRISPR/0AS9
SCREENS:
QUALITY
CONTROLS
.....................................
127
3.4.4
GENOME-WIDE
CRISPR/CAS9
SCREENS:
CANDIDATE
SELECTION
.............................
129
3.4.5
IDENTIFICATION
OF
APC
LOF
VULNERABILITIES
IN
HCT116
CELLS
.....................................
130
3.4.6
IDENTIFICATION
OF
VULNERABILITIES
OF
APC
L0F
RKO
CELLS
.........................................
133
3.4.7
IDENTIFICATION
OF
VULNERABILITIES
OF
APC
LOF
RKO
AND
ROT1
16
CELLS
.....................
136
3.4.8
SIRNA-BASED
ARRAY
SCREEN
FOR
CANDIDATE
VALIDATION
............................................
140
4
DISCUSSION
142
4.1
I
N
VITRO
CRC-
MODELS
OF
APC
LOSS
OF
FUNCTION
....................................................
142
4.2
I
NTERPLAY
BETWEEN
RAS
INHIBITION
AND
WNT
ACTIVATION
IN
CRC
.........................
145
4.3
MEK
INHIBITOR
TREATMENT
INDUCES
A
STEM
CELL
SIGNATURE
IN
CRC
CELLS
.............
147
4.4
E
NDOGENOUSLY
LABELED
FUNCTIONAL
B
-
CATENIN
PROTEINS
......................................
148
4.5
W
ILD
TYPE
AND
MUTANT
B
-
CATENIN
BELONG
TO
DIFFERENT
CELLULAR
POOLS
WITH
DISTINCT
DYNAMICS
........................................................................................................................................
151
4.6
F
UTURE
APPLICATIONS
OF
CTNNB1
KI
CELLS
...............................................................
154
4.7
I
NVESTIGATION
OF
APC
LOF
VULNERABILITIES
IN
COLORECTAL
CANCER
CELLS
............
155
5
MATERIAL
159
5.1
C
ELL
CULTURE
.............................................................................................................
159
5.1.1
CELL
LINES
................................................................................................................
159
5.1.2
PLASMIDS
................................................................................................................
159
5.1.3
SIRNAS
..................................................................................................................
160
5.1.4
PRIMERS
..................................................................................................................
161
5.1.5
ANTIBODIES
.............................................................................................................
164
5.1.6
BUFFERS
AND
SOLUTIONS
...........................................................................................
165
5.1.7
CONSUMABLES
AND
COMMERCIALLY
AVAILABLE
KITS
...................................................
166
6
METHODS
168
6.1
C
ELL
CULTURE
.............................................................................................................
168
6.1.1
T
RANSFECTIONS
........................................................................................................
168
6.2
W
ESTERN
B
LOT
TECHNIQUE
...........................................................................................
169
6.2.1
CO-IMMUNOPRECIPITATION
.......................................................................................
170
6.2.2
CYCLOHEXIMIDE
CHASE
ASSAY
.................................................................................
170
6.2.3
IMMUNOPRECIPITATION
AND
LIQUID-CHROMATOGRAPHY
MASS-SPECTROMETRY
(LC-MS)
170
6.3
L
IQUID
C
HROMATOGRAPHY
AND
MASS
SPECTROMETRY
ANALYSIS
...............................
171
6.4
G
ENERATION
OF
APC
TRUNCATED
ISOGENIC
CELL
LINES
.....................................................
172
6.4.1
SGRNAS
DESIGN
AND
CLONING
................................................................................
172
6.4.2
SGRNA
TRANSFECTION
AND
SINGLE
CELL
SERIAL
DILUTION
..............................................
173
6.5
G
ENERATION
OF
STABLE
CELL
LINES
...........................................................................
175
6.5.1
LENTIVIRAL
PARTICLE
PRODUCTION
...............................................................................
175
6.5.2
MOI
DETERMINATION:
ANTIBIOTIC
RESISTANT
CELLS
.......................................................
175
6.5.3
MOI
DETERMINATION:
TRANSGENE
(GFP)
EXPRESSING
CELLS
.....................................
176
6.5.4
STABLE
CELL
LINES
GENERATION
..................................................................................
176
6.6
WNT
REPORTER
ACTIVITY
ASSAY
................................................................................................
176
6.7
Q
UANTITATIVE
PCR
......................................................................................................
177
6.8
M
ICROSCOPY
-
BASED
ASSAYS
.......................................................................................
178
6.8.1
IMAGING
OF
FIXED
SAMPLES
.....................................................................................
178
2
6.8.2
LIVE
CELL
IMAGING:
SAMPLE
PREPARATION
................................................................
178
6.8.3
AUTOMATED
CELL
FIXATION,
STAINING
AND
IMAGING
....................................................
178
6.8.4
IMAGE
PROCESSING
AND
FEATURE
EXTRACTION
..........................................................
179
6.9
F
LUORESCENCE
CORRELATION
SPECTROSCOPY
(FCS)
...............................................
179
6.9.1
SAMPLE
PREPARATION
FOR
FCS
MEASUREMENTS
.....................................................
180
6.10
CRISPR-CAS9
SCREENING
.........................................................................................................
181
6.10.1
PLASMID
LIBRARY
GENERATION
...................................................................................
181
6.10.2
GENOME
WIDE
POOLED
KNOCK-OUT
SCREEN
.............................................................
182
6.11
S
TATISTICAL
ANALYSIS
.................................................................................................
184
3
|
| adam_txt |
TABLE
OF
CONTENT
LIST
OF
FIGURES
.
3
LIST
OF
TABLES
.
5
ABBREVIATIONS
.
7
ABSTRACT
.
8
ZUSAMMENFASSUNG
.
9
ACKNOWLEDGMENTS
.
11
1
INTRODUCTION
.
14
1.1
R
EGULATION
OF
SIGNAL
TRANSDUCTION
PATHWAYS
.
14
1.1.1
LIQUID-LIQUID
PHASE
SEPARATION
TUNES
SIGNAL
TRANSDUCTION
.
14
1.2
W
NT
SIGNALING
PATHWAY
.
15
1.2.1
THE
WNT/B-CATENIN
SIGNALING
PATHWAY
.
17
1.2.2
DUAL
ROLE
OF
B-CATENIN
PROTEIN
IN
SIGNAL
TRANSDUCTION
AND
ADHESION
.
21
1.2.3
WNT
SIGNALING
AND
COLORECTAL
CANCER
CARCINOGENESIS
.28
1.2.4
TARGETED
THERAPY
OF
THE
WNT
SIGNALING
PATHWAY
.
32
1.3
N
OVEL
METHODS
TO
INVESTIGATE
SIGNALING
PATHWAYS
.
35
1.3.1
RECOMBINANT
DNA
TECHNOLOGY:
GENOME
EDITING
NUCLEASES
.
35
2
AIMS
OF
THIS
STUDY
.
44
3
RESULTS
.46
3.1
I
N
VITRO
MODEL
OF
ARC
LOSS
OF
FUNCTION
COLORECTAL
CANCER
CELLS
.
46
3.1.1
ARC
IS
A
MULTIFUNCTIONAL
SCAFFOLD
PROTEIN
.
46
3.1.2
RKO
AND
HCT116
CELL
LINES
AS
SUITABLE
IN
VITRO
MODEL
OF
APC
LOF
.
49
3.1.3
GENERATION
AND
VALIDATION
OF
RKO
ISOGENIC
CELL
LINES
WITH
APC
L0F
MUTATIONS.
54
3.1.4
GENERATION
AND
VALIDATION
OF
HCT116
ISOGENIC
CELL
LINES
WITH
APC
LOF
MUTATIONS
57
3.1.5
APC
LOF
MUTATIONS
CHANGE
CELLULAR
MORPHOLOGY
.
58
3.2
MEK
INHIBITION
ACTIVATES
WNT
SIGNALING
IN
ORO
CELLS
.
63
3.2.1
RAS-ERK
AND
WNT
SIGNALING
MUTATIONS
IN
COLORECTAL
CANCER
.
63
3.2.2
SMALL
COMPOUND
CLASS
OF
MEK
INHIBITORS
AS
ACTIVATORS
OF
WNT/B-CATENIN
SIGNALING
65
3.2.3
TRAMETINIB
SYNERGIZES
WITH
CTNNB1
AND
APC
LOF
MUTATIONS
IN
THE
INDUCTION
OF
WNT
SIGNALING
.
67
3.2.4
MEK
INHIBITOR
INDUCES
A
DECREASE
OF
AXINL
STABILITY
.70
3.2.5
AXINL
E3
UBIQUITIN
LIGASES
ARE
NOT
INVOLVED
IN
WNT
SIGNALING
ACTIVATION
UPON
MEK
INHIBITION
.
73
3.2.6
TRANSCRIPTIONAL
REGULATION
OF
AXINL
BY
EGR1
.74
3.2.7
MEK
INHIBITION
IMPAIRS
THE
FORMATION
OF
AN
INTACT
AXINL
COMPLEX
.75
3.2.8
SYNERGISM
BETWEEN
MEK
AND
WNT
INHIBITION
IN
REPRESSING
CRC
TUMOR
GROWTH
77
3.3
E
NDOGENOUS
S
-
CATENIN
PROTEIN
TAGGING
.80
3.3.1
ENDOGENOUS
PROTEIN
TAGGING
USING
CRISPR-CAS9
TECHNOLOGY
.80
3.3.2
STRATEGY
DESIGN
OF
B-CATENIN
PROTEIN
TAGGING
.84
3.3.3
EVALUATION
OF
KNOCK-IN
EFFICIENCY
AT
THE
B-CATENIN
LOCUS
.87
3.3.4
SELECTION
AND
CHARACTERIZATION
OF
CTNNB1
KI
CELLS
.
91
3.3.5
FUNCTIONAL
CHARACTERIZATION
OF
ENDOGENOUSLY
TAGGED
B-CATENIN
CELL
LINES
.97
3.3.6
WILD-TYPE
AND
MUTANT
B-CATENIN
BELONGS
TO
TWO
DIFFERENT
POOLS
IN
THE
CELLS
.
106
3.3.7
CHARACTERIZATION
OF
B-CATENIN
SPATIAL
DYNAMICS
IN
LIVE
CELLS
USING
FLUORESCENCE
CORRELATION
SPECTROSCOPY
(FCS)
.
111
3.4
T
OWARDS
IDENTIFICATION
OF
ARC
LOSS
OF
FUNCTION
VULNERABILITIES
.
123
3.4.1
CRISPR/CAS9
FUNCTIONAL
GENETIC
SCREENS
.
123
3.4.2
GENOME-WIDE
CRISPR/CAS9
SCREEN
IN
ISOGENIC
CRC
CELLS
.
125
3.4.3
GENOME-WIDE
CRISPR/0AS9
SCREENS:
QUALITY
CONTROLS
.
127
3.4.4
GENOME-WIDE
CRISPR/CAS9
SCREENS:
CANDIDATE
SELECTION
.
129
3.4.5
IDENTIFICATION
OF
APC
LOF
VULNERABILITIES
IN
HCT116
CELLS
.
130
3.4.6
IDENTIFICATION
OF
VULNERABILITIES
OF
APC
L0F
RKO
CELLS
.
133
3.4.7
IDENTIFICATION
OF
VULNERABILITIES
OF
APC
LOF
RKO
AND
ROT1
16
CELLS
.
136
3.4.8
SIRNA-BASED
ARRAY
SCREEN
FOR
CANDIDATE
VALIDATION
.
140
4
DISCUSSION
142
4.1
I
N
VITRO
CRC-
MODELS
OF
APC
LOSS
OF
FUNCTION
.
142
4.2
I
NTERPLAY
BETWEEN
RAS
INHIBITION
AND
WNT
ACTIVATION
IN
CRC
.
145
4.3
MEK
INHIBITOR
TREATMENT
INDUCES
A
STEM
CELL
SIGNATURE
IN
CRC
CELLS
.
147
4.4
E
NDOGENOUSLY
LABELED
FUNCTIONAL
B
-
CATENIN
PROTEINS
.
148
4.5
W
ILD
TYPE
AND
MUTANT
B
-
CATENIN
BELONG
TO
DIFFERENT
CELLULAR
POOLS
WITH
DISTINCT
DYNAMICS
.
151
4.6
F
UTURE
APPLICATIONS
OF
CTNNB1
KI
CELLS
.
154
4.7
I
NVESTIGATION
OF
APC
LOF
VULNERABILITIES
IN
COLORECTAL
CANCER
CELLS
.
155
5
MATERIAL
159
5.1
C
ELL
CULTURE
.
159
5.1.1
CELL
LINES
.
159
5.1.2
PLASMIDS
.
159
5.1.3
SIRNAS
.
160
5.1.4
PRIMERS
.
161
5.1.5
ANTIBODIES
.
164
5.1.6
BUFFERS
AND
SOLUTIONS
.
165
5.1.7
CONSUMABLES
AND
COMMERCIALLY
AVAILABLE
KITS
.
166
6
METHODS
168
6.1
C
ELL
CULTURE
.
168
6.1.1
T
RANSFECTIONS
.
168
6.2
W
ESTERN
B
LOT
TECHNIQUE
.
169
6.2.1
CO-IMMUNOPRECIPITATION
.
170
6.2.2
CYCLOHEXIMIDE
CHASE
ASSAY
.
170
6.2.3
IMMUNOPRECIPITATION
AND
LIQUID-CHROMATOGRAPHY
MASS-SPECTROMETRY
(LC-MS)
170
6.3
L
IQUID
C
HROMATOGRAPHY
AND
MASS
SPECTROMETRY
ANALYSIS
.
171
6.4
G
ENERATION
OF
APC
TRUNCATED
ISOGENIC
CELL
LINES
.
172
6.4.1
SGRNAS
DESIGN
AND
CLONING
.
172
6.4.2
SGRNA
TRANSFECTION
AND
SINGLE
CELL
SERIAL
DILUTION
.
173
6.5
G
ENERATION
OF
STABLE
CELL
LINES
.
175
6.5.1
LENTIVIRAL
PARTICLE
PRODUCTION
.
175
6.5.2
MOI
DETERMINATION:
ANTIBIOTIC
RESISTANT
CELLS
.
175
6.5.3
MOI
DETERMINATION:
TRANSGENE
(GFP)
EXPRESSING
CELLS
.
176
6.5.4
STABLE
CELL
LINES
GENERATION
.
176
6.6
WNT
REPORTER
ACTIVITY
ASSAY
.
176
6.7
Q
UANTITATIVE
PCR
.
177
6.8
M
ICROSCOPY
-
BASED
ASSAYS
.
178
6.8.1
IMAGING
OF
FIXED
SAMPLES
.
178
2
6.8.2
LIVE
CELL
IMAGING:
SAMPLE
PREPARATION
.
178
6.8.3
AUTOMATED
CELL
FIXATION,
STAINING
AND
IMAGING
.
178
6.8.4
IMAGE
PROCESSING
AND
FEATURE
EXTRACTION
.
179
6.9
F
LUORESCENCE
CORRELATION
SPECTROSCOPY
(FCS)
.
179
6.9.1
SAMPLE
PREPARATION
FOR
FCS
MEASUREMENTS
.
180
6.10
CRISPR-CAS9
SCREENING
.
181
6.10.1
PLASMID
LIBRARY
GENERATION
.
181
6.10.2
GENOME
WIDE
POOLED
KNOCK-OUT
SCREEN
.
182
6.11
S
TATISTICAL
ANALYSIS
.
184
3 |
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| author | Ambrosi, Giulia 1988- |
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| discipline | Chemie / Pharmazie Biologie |
| discipline_str_mv | Chemie / Pharmazie Biologie |
| format | Thesis Book |
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| spelling | Ambrosi, Giulia 1988- Verfasser (DE-588)1189461374 aut Investigation of aberrant WNT signaling in colorectal cancer cells Giulia Ambrosi Heidelberg 2019 218 Seiten Illustrationen, Diagramme txt rdacontent n rdamedia nc rdacarrier Dissertation Ruperto-Carola University of Heidelberg, Germany 2019 (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf https://d-nb.info/1217737995/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=032339956&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Ambrosi, Giulia 1988- Investigation of aberrant WNT signaling in colorectal cancer cells |
| subject_GND | (DE-588)4113937-9 |
| title | Investigation of aberrant WNT signaling in colorectal cancer cells |
| title_auth | Investigation of aberrant WNT signaling in colorectal cancer cells |
| title_exact_search | Investigation of aberrant WNT signaling in colorectal cancer cells |
| title_exact_search_txtP | Investigation of aberrant WNT signaling in colorectal cancer cells |
| title_full | Investigation of aberrant WNT signaling in colorectal cancer cells Giulia Ambrosi |
| title_fullStr | Investigation of aberrant WNT signaling in colorectal cancer cells Giulia Ambrosi |
| title_full_unstemmed | Investigation of aberrant WNT signaling in colorectal cancer cells Giulia Ambrosi |
| title_short | Investigation of aberrant WNT signaling in colorectal cancer cells |
| title_sort | investigation of aberrant wnt signaling in colorectal cancer cells |
| topic_facet | Hochschulschrift |
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