Evi-Wls mediated Wnt secretion is required for colon cancer growth and survival despite APC or beta-catenin mutations:
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| 1. Verfasser: | |
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| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
2012
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| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | Zsfassung in dt. Sprache |
| Beschreibung: | IV, 115, X Sp. Ill., graph. Darst. |
Internformat
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| 245 | 1 | 0 | |a Evi-Wls mediated Wnt secretion is required for colon cancer growth and survival despite APC or beta-catenin mutations |c presented by Gerrit Erdmann |
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Datensatz im Suchindex
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| adam_text | TABLE OF CONTENTS
ACKNOWLEDEGMENTS I
TABLE OF CONTENTS II
SUMMARY 1
ZUSAMMENFASSUNG 2
1 INTRODUCTION 4
1.1 STRUCTURE AND HOMEOSTASIS OF THE INTESTINE 5
1.2 SIGNALING PATHWAYS
IN INTESTINAL HOMEOSTASIS 8
1.2.1 WNT SIGNALING 9
1.2.2 WNT STRUCTURE AND EVI/WLS MEDIATED
SECRETION 12
1.2.3 WNT/P-CATENIN SIGNALING IN THE INTESTINE 14
1.2.4 OTHER SIGNALING PATHWAYS
IN THE INTESTINE 15
1.3 COLORECTAL CANCER
DEVELOPMENT 18
1.3.1 FAMILIAL ADENOMATOUS POLYPOSIS
(FAP) 19
1.3.2 SPORADIC COLORECTAL CANCER 19
1.4 MECHANISM OF WNT PATHWAY MUTATIONS IN COLORECTAL CANCER 22
1.5 AIM OF THE THESIS 24
2 RESULTS 26
2.1 WNT SECRETION IS REQUIRED FOR WNT/FL-CATENIN TARGET GENE EXPRESSION
IN COLON CANCER
CELLS DESPITE ACTIVATING MUTATIONS 26
2.1.1 KNOCKDOWN OF WNT-SIGNALING
PATHWAY COMPONENTS 28
2.1.2 SEQUENCING AND
MAPPING 28
2.1.3 ATCT/S45 FT-CATENIN IS PREDOMINANTLY
EXPRESSED IN HCT116
CELLS 34
2.1.4 GENE EXPRESSION PROFILING
INDICATES REGULATION UPSTREAM OF MUTANT 0-CATENIN 35
2.1.5 NEM STRONGLY FAVORS PATHWAY
TOPOLOGIES THAT ALLOW REGULATION UPSTREAM OF
P-CATENIN 37
2.2 WNT SECRETION IS REQUIRED FOR CANONICAL WNT/FS-CATENIN SIGNALING
DESPITE 9-CATENIN AND
APC MUTATIONS 38
2.2.1 EVI/WLS IS REQUIRED FOR WNT PATHWAY ACTIVITY IN HCT116 CELLS
DESPITE
MUTATIONS IN
F)-CATENIN 39
2.2.2 OVEREXPRESSION OF EVI/WLS
RESCUES WNT PATHWAY ACTIVITY AFTER EVI/WLS KNOCKDOWN
42
2.2.3 CELLS WITH APC MUTATION
REQUIRE EVI/WLS FOR PATHWAY ACTIVATION 44
2.2.4 SECRETION OF CANONICAL WNT BY EVI/WLS IS REQUIRED FOR WNT PATHWAY
ACTIVATION IN
APC AND FI-CATENIN MUTANT
CELLS 46
II
HTTP://D-NB.INFO/1044695315
2.3 WNT SECRETION IS REQUIRED FOR COLON CANCER CELL
GROWTH AND SURVIVAL IN VITRO AND IN VIVO50
2.3.1 EVI/WLS IS REQUIRED
FOR SHORT AND LONG TERM SURVIVAL OF COLON CANCER CELLS SO
2.3.2 KNOCKDOWN OF EVI/WLS REDUCED
TUMOR GROWTH IN MOUSE
XENOGRAFTS 52
2.3.3 EVI/WLS AND WNT3 ARE
OVEREXPRESSED IN COLON TUMORS CORRELATING WITH DECREASED
SURVIVAL 55
2.4 ARC AND P-CATENIN MUTATIONS SENSITIIE TO WNT LIGANDS 59
2.4.1 TRUNCATED APC IS STILL BOUND TO THE DESTRUCTION COMPLEX 59
2.4.2 AS45/TCT P-CATENIN CAN
STILL BE PHOSPHORYLATED AT SUBSEQUENT RESIDUES 61
2.4.3 PARTIAL DEPLETION OF APC SENSITIZES COLON
CANCER CELLS TO WNT3A 63
2.5 CONCLUSION 65
3 DISCUSSION 66
3.1 EVI/WLS MEDIATED WNT SECRETION IS REQUIRED FOR CANONICAL WNT PATHWAY
ACTIVATION IN
CELL LINES WITH P-CATENIN MUTATIONS 67
3.2 EVI/WLS MEDIATED WNT SECRETION IS REQUIRED FOR WNT/0-CATENLN PATHWAY
ACTIVATION IN
CELL LINES WITH APC MUTATIONS 70
3.2.1 ADDITIONAL ROLES OF APC IN COLORECTAL
CARCINOGENESIS 73
3.3 EVI/WLS MEDIATED WNT SECRETION IS REQUIRED FOR COLORECTAL CANCER IN
VITRO AND IN VIVO.. 74
3.4 WNT SIGNALING AND COLORECTAL CARCINOGENESIS 78
3.4.1 IMPACTS ON THERAPY 79
3.4.2 OTHER COLORECTAL CANCER SYNDROMES 81
3.5 CONCLUSION AND OUTLOOK 82
4 MATERIALS AND METHODS 85
4.1 MATERIALS 85
4.1.1 MEDIA AND BUFFERS 85
4.1.2 ANTIBODIES 88
4.1.3 SIRNA REAGENTS 89
4.1.4 QRT-PCR PRIMERS 89
4.2 METHODS 90
4.2.1 MOLECULAR CLONING 90
4.2.2 CELL CULTURE AND
CELL BASED ASSAYS 91
4.2.3 SEQUENCING EXPERIMENTS 97
4.2.4 IN VIVO
EXPERIMENTS 98
5 LITERATURE 101
III
6 APPENDIX I
6.1 NESTED EFFECT MODELLING AND BAYES FACTOR BASED MODEL SELECTION I
6.2 TABLE OF FIGURES IX
6.3 PUBLICATIONS DERIVED OF THIS WORK X
IV
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| ctrlnum | (OCoLC)867148369 (DE-599)BSZ396891055 |
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| illustrated | Illustrated |
| indexdate | 2024-07-10T00:57:01Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-026898325 |
| oclc_num | 867148369 |
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| physical | IV, 115, X Sp. Ill., graph. Darst. |
| publishDate | 2012 |
| publishDateSearch | 2012 |
| publishDateSort | 2012 |
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| spelling | Erdmann, Gerrit Verfasser (DE-588)1044338261 aut Evi-Wls mediated Wnt secretion is required for colon cancer growth and survival despite APC or beta-catenin mutations presented by Gerrit Erdmann 2012 IV, 115, X Sp. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Zsfassung in dt. Sprache Heidelberg, Univ., Diss., 2012 Colonkrebs (DE-588)4148225-6 gnd rswk-swf Wnt-Proteine (DE-588)7515809-7 gnd rswk-swf (DE-588)4113937-9 Hochschulschrift gnd-content Colonkrebs (DE-588)4148225-6 s Wnt-Proteine (DE-588)7515809-7 s DE-604 DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026898325&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Erdmann, Gerrit Evi-Wls mediated Wnt secretion is required for colon cancer growth and survival despite APC or beta-catenin mutations Colonkrebs (DE-588)4148225-6 gnd Wnt-Proteine (DE-588)7515809-7 gnd |
| subject_GND | (DE-588)4148225-6 (DE-588)7515809-7 (DE-588)4113937-9 |
| title | Evi-Wls mediated Wnt secretion is required for colon cancer growth and survival despite APC or beta-catenin mutations |
| title_auth | Evi-Wls mediated Wnt secretion is required for colon cancer growth and survival despite APC or beta-catenin mutations |
| title_exact_search | Evi-Wls mediated Wnt secretion is required for colon cancer growth and survival despite APC or beta-catenin mutations |
| title_full | Evi-Wls mediated Wnt secretion is required for colon cancer growth and survival despite APC or beta-catenin mutations presented by Gerrit Erdmann |
| title_fullStr | Evi-Wls mediated Wnt secretion is required for colon cancer growth and survival despite APC or beta-catenin mutations presented by Gerrit Erdmann |
| title_full_unstemmed | Evi-Wls mediated Wnt secretion is required for colon cancer growth and survival despite APC or beta-catenin mutations presented by Gerrit Erdmann |
| title_short | Evi-Wls mediated Wnt secretion is required for colon cancer growth and survival despite APC or beta-catenin mutations |
| title_sort | evi wls mediated wnt secretion is required for colon cancer growth and survival despite apc or beta catenin mutations |
| topic | Colonkrebs (DE-588)4148225-6 gnd Wnt-Proteine (DE-588)7515809-7 gnd |
| topic_facet | Colonkrebs Wnt-Proteine Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026898325&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT erdmanngerrit eviwlsmediatedwntsecretionisrequiredforcoloncancergrowthandsurvivaldespiteapcorbetacateninmutations |