uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
The transcription factor MAFK induces EMT and malignant progression of triple-negative breast cancer cells through its target GPNMB
Univ Tsukuba, Grad Sch Comprehens Human Sci, Dept Expt Pathol, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan.;Univ Tsukuba, Fac Med, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan..
Univ Tsukuba, Grad Sch Comprehens Human Sci, Dept Expt Pathol, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan.;Univ Tsukuba, Fac Med, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan..
Univ Tsukuba, Grad Sch Comprehens Human Sci, Dept Expt Pathol, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan.;Univ Tsukuba, Fac Med, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan..
Univ Tsukuba, Grad Sch Comprehens Human Sci, Dept Expt Pathol, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan.;Univ Tsukuba, Fac Med, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan..
Show others and affiliations
2017 (English)In: Science Signaling, ISSN 1945-0877, E-ISSN 1937-9145, Vol. 10, no 474, eaak9397Article in journal (Refereed) Published
Abstract [en]

Triple-negative breast cancer (TNBC) is particularly aggressive and difficult to treat. For example, the transforming growth factor-beta (TGF-beta) pathway is implicated in TNBC progression and metastasis, but its opposing role in tumor suppression in healthy tissues and early-stage lesions makes it a challenging target. Therefore, additional molecular characterization of TNBC may lead to improved patient prognosis by informing the development and optimum use of targeted therapies. We found that musculoaponeurotic fibrosarcoma (MAF) oncogene family protein K (MAFK), a member of the small MAF family of transcription factors that are induced by the TGF-beta pathway, was abundant in human TNBC and aggressive mouse mammary tumor cell lines. MAFK promoted tumorigenic growth and metastasis by 4T1 cells when implanted subcutaneously in mice. Overexpression of MAFK in mouse breast epithelial NMuMG cells induced epithelial-mesenchymal transition (EMT) phenotypes and promoted tumor formation and invasion in mice. MAFK induced the expression of the gene encoding the transmembrane glycoprotein nmb(GPNMB). Similar to MAFK, GPNMB overexpression in NMuMG cells induced EMT, tumor formation, and invasion, in mice, whereas knockdown of MAFK in tumor cells before implantation suppressed tumor growth and progression. MAFK and GPNMB expression correlated with poor prognosis in TNBC patients. These findings suggest that MAFK and its target gene GPNMB play important roles in the malignant progression of TNBC cells, offering potentially new therapeutic targets for TNBC patients.

Place, publisher, year, edition, pages
AMER ASSOC ADVANCEMENT SCIENCE , 2017. Vol. 10, no 474, eaak9397
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-321838DOI: 10.1126/scisignal.aak9397ISI: 000398836400003OAI: oai:DiVA.org:uu-321838DiVA: diva2:1095666
Funder
Swedish Research Council, 2015-02757
Available from: 2017-05-15 Created: 2017-05-15 Last updated: 2017-05-15Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Heldin, Carl-Henrik
By organisation
Ludwig Institute for Cancer ResearchScience for Life Laboratory, SciLifeLab
In the same journal
Science Signaling
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 172 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf