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Göteborgs universitets publikationer

Nuclear Janus-activated kinase 2/nuclear factor 1-C2 suppresses tumorigenesis and epithelial-to-mesenchymal transition by repressing Forkhead box F1.

Författare och institution:
Jeanette Nilsson (Institutionen för cell- och molekylärbiologi, molekylärbiologi); Khalil Helou (Institutionen för kliniska vetenskaper, sektionen för onkologi, radiofysik, radiologi och urologi, Avdelningen för onkologi); Anikó Kovács (-); Pär-Ola Bendahl (-); Gunnar Bjursell (Institutionen för cell- och molekylärbiologi, molekylärbiologi); Mårten Fernö (-); Peter Carlsson (Institutionen för cell- och molekylärbiologi); Marie Kannius-Janson (Institutionen för cell- och molekylärbiologi, molekylärbiologi)
Publicerad i:
Cancer research, 70 ( 5 ) s. 2020-2029
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Progression to metastasis is the proximal cause of most cancer-related mortality. Yet much remains to be understood about what determines the spread of tumor cells. This paper describes a novel pathway in breast cancer that regulates epithelial-to-mesenchymal transition (EMT), motility, and invasiveness. We identify two transcription factors, nuclear factor 1-C2 (NF1-C2) and Forkhead box F1 (FoxF1), downstream of prolactin/nuclear Janus-activated kinase 2, with opposite effects on these processes. We show that NF1-C2 is lost during mammary tumor progression and is almost invariably absent from lymph node metastases. NF1-C2 levels in primary tumors correlate with better patient survival. Manipulation of NF1-C2 levels by expression of a stabilized version or using small interfering RNA showed that NF1-C2 counteracts EMT, motility, invasiveness, and tumor growth. FoxF1 was found to be a direct repressed target of NF1-C2. We provide the first evidence for a role of FoxF1 in cancer and in the regulation of EMT in cells of epithelial origin. Overexpression of FoxF1 was associated with a mesenchymal phenotype, increased invasiveness in vitro, and enhanced growth of breast carcinoma xenografts in nude mice. The relevance of these findings is strengthened by the correlation between FoxF1 expression and a mesenchymal phenoype in breast cancer cell isolates, consistent with the interpretation that FoxF1 promotes invasion and metastasis.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Klinisk medicin ->
Cancer och onkologi
Animals, Breast Neoplasms, genetics, metabolism, pathology, Cell Adhesion, physiology, Cell Growth Processes, physiology, Cell Line, Tumor, Cell Movement, physiology, Epithelial Cells, pathology, Female, Forkhead Transcription Factors, antagonists & inhibitors, biosynthesis, genetics, metabolism, Humans, Janus Kinase 2, metabolism, Mesoderm, pathology, Mice, Mice, Inbred BALB C, Mice, Nude, NFI Transcription Factors, metabolism, Promoter Regions, Genetic
Postens nummer:
Posten skapad:
2011-01-19 14:44
Posten ändrad:
2012-01-18 15:37

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