Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

The microRNA-200 family as regulators of breast and colorectal tumour metastasis (#104)

Philip A Gregory 1 2 , Xiaochun Li 1 , Emily L Paterson 1 , Suraya Roslan 1 , Cameron P Bracken 1 2 , Josephine A Wright 1 2 , Andrew G Bert 1 , Matthew J Anderson 1 , Cameron N Johnstone 3 , Robin L Anderson 3 , Gregory J Goodall 1 2 4 , Yeesim Khew-Goodall 1 4
  1. Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, Australia
  2. Discipline of Medicine, The University of Adelaide, Adelaide, South Australia, Australia
  3. Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
  4. School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, South Australia, Australia

The miR-200 family plays a critical role in maintaining the epithelial phenotype through repression of the E-cadherin regulating transcription factors ZEB1 and ZEB2 (1,2,3). Loss of the miR-200 family has been shown to lead to an epithelial-mesenchymal transition (EMT) with an associated increase in invasive capacity suggesting it may play a regulatory role in tumour metastasis. We have examined the expression and function of individual miR-200 family members in two distinct models of tumour metastasis– (1) A xenograft model of spontaneous breast cancer metastasis and (2) Human colorectal adenocarcinomas. Stable expression of miR-200b or miR-200c, but not miR-141, in the MDA-MB-231 (LM2) subline attenuated the ability of these cells to metastasise from the mammary fat pad. Interestingly, restoration of ZEB1 expression in miR-200b stable cells was not sufficient to alleviate metastatic repression, but instead several cytoskeletal associated miR-200 targets appear to also contribute to cell invasion from the primary tumour. In human colorectal adenocarcinomas, in situ hybridization and laser capture microscopy revealed the expression of miR-200b and miR-200c is specifically reduced at the invasive front of colorectal adenocarcinomas that have destroyed and invaded beyond the basement membrane. Examination of regional lymph node metastases in these samples show strong expression of miR-200, indicating this family of miRNAs can induce a mesenchymal to epithelial transition (MET) and recapitulate the primary tumour phenotype at metastatic sites. Taken together, these data support a regulatory role for the miR-200 family in controlling EMT/MET and tumour metastasis in breast and colorectal carcinomas.

  1. Gregory PA et al (2008) Nature Cell Biol. 10, 593-601.
  2. Bracken CP et al (2008) Cancer Res. 68, 7846-7854.
  3. Gregory PA et al (2011) Mol. Biol. Cell. 22, 1686-1698.