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

Direct link
HS3ST2 modulates breast cancer cell invasiveness via MAP kinase- and Tcf4 (Tcf7l2)-dependent regulation of protease and cadherin expression
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
Show others and affiliations
2014 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 11, 2579-2592 p.Article in journal (Refereed) Published
Abstract [en]

Heparan sulfate 3-O-sulfotransferase 2 (HS3ST2), an enzyme mediating 3-O-sulfation of heparan sulfate (HS), is silenced by hypermethylation in breast cancer. As HS has an important co-receptor function for numerous signal transduction pathways, the phenotypical changes due to HS3ST2 reexpression were investigated in vitro using high and low invasive breast cancer cell lines. Compared to controls, highly invasive HS3ST2-expressing MDA-MB-231 cells showed enhanced Matrigel invasiveness, transendothelial migration and motility. Affymetrix screening and confirmatory real-time PCR and Western blotting analysis revealed increased expression of several matrix metalloproteinases, cadherin-11, E-cadherin and CEACAM-1, while protease inhibitor and annexin A10 expression were decreased. Low invasive HS3ST2 -expressing MCF-7 cells became even less invasive, with no change in gelatinolytic MMP activity. HS3ST2 expression increased HS-dependent basal and FGF2-specific signaling through the constitutively active p44/42 MAPK pathway in MDA-MB-231 cells. Increased MAPK activation was accompanied by upregulation of beta-catenin in MDA-MB-231, and of the transcription factor Tcf4 in both cell lines. Dysregulation of Tcf4-regulated ion transporters and increased cytosolic acidification were observed in HS3ST2-expressing MDA-MB-231 cells, which is a possible underlying cause of increased chemosensitivity towards doxorubicine and paclitaxel in these cells. This study provides the first in vitro evidence of the involvement of HS3ST2 in breast cancer cell invasion and chemosensitivity.

Place, publisher, year, edition, pages
2014. Vol. 135, no 11, 2579-2592 p.
Keyword [en]
heparan sulfate, metastasis, chemosensitivity, glycosaminoglycan, cadherin, signal transduction, invasiveness
National Category
Cancer and Oncology
URN: urn:nbn:se:uu:diva-236026DOI: 10.1002/ijc.28921ISI: 000342811800010PubMedID: 24752740OAI: oai:DiVA.org:uu-236026DiVA: diva2:762992
Available from: 2014-11-13 Created: 2014-11-12 Last updated: 2014-11-13Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Spillmann, Dorothe
By organisation
Department of Medical Biochemistry and Microbiology
In the same journal
International Journal of Cancer
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 281 hits
ReferencesLink to record
Permanent link

Direct link