Tenascin-C downregulates wnt inhibitor dickkopf-1, promoting tumorigenesis in a neuroendocrine tumor model

Saupe, Falk; Schwenzer, Anja; Jia, Yundan; Gasser, Isabelle; Spenlé, Caroline; Langlois, Benoit; Kammerer, Martial; Lefebvre, Olivier; Hlushchuk, Ruslan; Rupp, Tristan; Marko, Marija; van der Heyden, Michael; Cremel, Gérard; Arnold, Christiane; Klein, Annick; Simon-Assmann, Patricia; Djonov, Valentin; Neuville-Méchine, Agnès; Esposito, Irene; Slotta-Huspenina, Julia; ... (2013). Tenascin-C downregulates wnt inhibitor dickkopf-1, promoting tumorigenesis in a neuroendocrine tumor model. Cell reports, 5(2), pp. 482-492. Cell Press 10.1016/j.celrep.2013.09.014

[img]
Preview
Text
1-s2.0-S2211124713005226-main.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (2MB) | Preview

The extracellular matrix molecule tenascin-C (TNC) is a major component of the cancer-specific matrix, and high TNC expression is linked to poor prognosis in several cancers. To provide a comprehensive understanding of TNC's functions in cancer, we established an immune-competent transgenic mouse model of pancreatic β-cell carcinogenesis with varying levels of TNC expression and compared stochastic neuroendocrine tumor formation in abundance or absence of TNC. We show that TNC promotes tumor cell survival, the angiogenic switch, more and leaky vessels, carcinoma progression, and lung micrometastasis. TNC downregulates Dickkopf-1 (DKK1) promoter activity through the blocking of actin stress fiber formation, activates Wnt signaling, and induces Wnt target genes in tumor and endothelial cells. Our results implicate DKK1 downregulation as an important mechanism underlying TNC-enhanced tumor progression through the provision of a proangiogenic tumor microenvironment.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Topographical and Clinical Anatomy

UniBE Contributor:

Hlushchuk, Ruslan and Djonov, Valentin

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2211-1247

Publisher:

Cell Press

Language:

English

Submitter:

Beatrice Itten

Date Deposited:

04 Apr 2014 18:47

Last Modified:

24 Dec 2014 00:31

Publisher DOI:

10.1016/j.celrep.2013.09.014

PubMed ID:

24139798

BORIS DOI:

10.7892/boris.39390

URI:

https://boris.unibe.ch/id/eprint/39390

Actions (login required)

Edit item Edit item
Provide Feedback