The role of S100a4 (Mts1) in Apc- and Smad4-driven tumour onset and progression

Yaser Atlasi, Rubina Noori, Ivana Marolin, Patrick Franken, Joana Brandao, Katharina Biermann, Paola Collini, Mariam Grigorian, Eugene Lukanidin, Noona Ambartsumian, Riccardo Fodde

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

INTRODUCTION: S100a4 is a calcium-binding protein belonging to the family of S100-proteins, highly expressed in different stromal cell types. S100A4 has been reported as a prognostic marker in colorectal cancer in association with tumour progression and metastasis.

METHODS: In this study, we analysed the in vivo role of S100a4 in intestinal tumour initiation and progression using different transgenic and knockout mouse models.

RESULTS: We found that genetic ablation or overexpression of S100a4 in both Apc- and Smad4-mutant mice do not affect tumour initiation in the intestinal tract. In contrast, S100a4 epithelial overexpression in Apc1638N/+/KRASV12G mice increases the dissemination of intestinal tumour cells to the liver, in agreement with its role in tumour metastasis. Moreover, we report a novel role for S100a4 in desmoid formation where S100a4 deficiency results in a significant reduction of the tumour burden characteristic of the Apc1638N model. In agreement with these results, S100a4 appears to be co-expressed together with mesenchymal stem cell (MSC) markers in desmoid tumours from Apc1638N/+ mice, as well as from sporadic and hereditary human desmoids.

CONCLUSION: Our data provide the first report on the in vivo role of S100a4 in intestinal tumourigenesis and describe a new role for S100a4 in the aetiology of desmoids formation.

Original languageEnglish
Pages (from-to)114-124
Number of pages11
JournalEuropean journal of cancer (Oxford, England : 1990)
Volume68
DOIs
Publication statusPublished - 14 Oct 2016

Keywords

  • Adenomatous Polyposis Coli Protein/genetics
  • Animals
  • Carcinogenesis/genetics
  • Colorectal Neoplasms/genetics
  • Fibromatosis, Aggressive/genetics
  • Gene Knock-In Techniques
  • Humans
  • Intestinal Neoplasms/genetics
  • Mice
  • Mice, Knockout
  • Mutation
  • Proto-Oncogene Proteins p21(ras)/genetics
  • S100 Calcium-Binding Protein A4/genetics
  • Smad4 Protein/genetics

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