PMID- 21173432
OWN - NLM
STAT- MEDLINE
DCOM- 20110523
LR  - 20220223
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Linking)
VI  - 32
IP  - 3
DP  - 2011 Mar
TI  - beta-catenin-independent WNT signaling in basal-like breast cancer and brain 
      metastasis.
PG  - 434-42
LID - 10.1093/carcin/bgq269 [doi]
AB  - A role of WNT signaling for primary breast cancers of the basal-like subtype and 
      as a predictor of brain metastasis has been described. However, a responsible WNT 
      ligand has not been identified. To further clarify this question, we 
      comparatively investigated 22 human breast cancer brain metastases as well as the 
      highly invasive human breast cancer cell line MDA-MB-231 and the weakly motile 
      MCF-7 as models for the basal-like and the luminal A subtype. WNT5A and B were 
      found overexpressed in MDA-MB-231 cells as compared with MCF-7. This corresponded 
      to reduction of MDA-MB-231 invasiveness by WNT inhibitors, whereas MCF-7 invasion 
      was enhanced by recombinant WNT5B and abolished by WNT and Jun-N-terminal kinase 
      antagonists. Expression and subcellular distribution of beta-catenin remained 
      uninfluenced. Consistently, beta-catenin was not localized in the nuclei of brain 
      metastases while there was strong nuclear c-Jun staining. Similar to MDA-MB-231, 
      metastases showed expression of WNT5A/B and the alternative WNT receptors ROR1 
      and 2. These findings were validated using external gene expression datasets 
      (Gene Expression Omnibus) of different breast cancer subtypes and brain 
      metastases. Hierarchical cluster analysis yielded a close relation between 
      basal-like cancers and brain metastases. Gene set enrichment analyses confirmed 
      WNT pathway enrichment not only in basal-like primaries but also in cerebral 
      metastases of all subtypes. In conclusion, WNT signaling seems highly relevant 
      for basal-like and other subtypes of breast cancers metastasizing into the brain. 
      beta-catenin-independent WNT signaling, presumably via ROR1-2, plays a major role in 
      this context.
FAU - Klemm, F
AU  - Klemm F
AD  - Department of Hematology/Oncology, University of Gottingen, 37099 Gottingen, 
      Germany.
FAU - Bleckmann, A
AU  - Bleckmann A
FAU - Siam, L
AU  - Siam L
FAU - Chuang, H N
AU  - Chuang HN
FAU - Rietkotter, E
AU  - Rietkotter E
FAU - Behme, D
AU  - Behme D
FAU - Schulz, M
AU  - Schulz M
FAU - Schaffrinski, M
AU  - Schaffrinski M
FAU - Schindler, S
AU  - Schindler S
FAU - Trumper, L
AU  - Trumper L
FAU - Kramer, F
AU  - Kramer F
FAU - Beissbarth, T
AU  - Beissbarth T
FAU - Stadelmann, C
AU  - Stadelmann C
FAU - Binder, C
AU  - Binder C
FAU - Pukrop, T
AU  - Pukrop T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101220
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (WNT5A protein, human)
RN  - 0 (WNT5B protein, human)
RN  - 0 (Wnt Proteins)
RN  - 0 (Wnt-5a Protein)
RN  - 0 (beta Catenin)
SB  - IM
MH  - Apoptosis
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Brain Neoplasms/*genetics/secondary
MH  - Breast Neoplasms/*genetics/pathology
MH  - Carcinoma, Basal Cell/genetics/pathology
MH  - Cell Adhesion
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Female
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Oligonucleotide Array Sequence Analysis
MH  - Proto-Oncogene Proteins/*genetics
MH  - RNA, Messenger/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Wnt Proteins/*genetics
MH  - Wnt-5a Protein
MH  - beta Catenin/*genetics
EDAT- 2010/12/22 06:00
MHDA- 2011/05/24 06:00
CRDT- 2010/12/22 06:00
PHST- 2010/12/22 06:00 [entrez]
PHST- 2010/12/22 06:00 [pubmed]
PHST- 2011/05/24 06:00 [medline]
AID - bgq269 [pii]
AID - 10.1093/carcin/bgq269 [doi]
PST - ppublish
SO  - Carcinogenesis. 2011 Mar;32(3):434-42. doi: 10.1093/carcin/bgq269. Epub 2010 Dec 
      20.