MiR-200 can repress breast cancer metastasis through ZEB1-independent but moesin-dependent pathways

X Li; S Roslan; CN Johnstone; JA Wright; CP Bracken; M Anderson; AG Bert; LA Selth; RL Anderson; GJ Goodall; PA Gregory; Y Khew-Goodall

Journal article

MiR-200 can repress breast cancer metastasis through ZEB1-independent but moesin-dependent pathways

X Li, S Roslan, CN Johnstone, JA Wright, CP Bracken, M Anderson, AG Bert, LA Selth, RL Anderson, GJ Goodall, PA Gregory, Y Khew-Goodall

Oncogene | Published : 2014

DOI: 10.1038/onc.2013.370

Abstract

The microRNA-200 (miR-200) family has a critical role in regulating epithelial-mesenchymal transition and cancer cell invasion through inhibition of the E-cadherin transcriptional repressors ZEB1 and ZEB2. Recent studies have indicated that the miR-200 family may exert their effects at distinct stages in the metastatic process, with an overall effect of enhancing metastasis in a syngeneic mouse breast cancer model. We find in a xenograft orthotopic model of breast cancer metastasis that ectopic expression of members of the miR-200b/200c/429, but not the miR-141/200a, functional groups limits tumour cell invasion and metastasis. Despite modulation of the ZEB1-E-cadherin axis, restoration of Z..

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University of Melbourne Researchers

Robin Anderson Author

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Grants

Awarded by Prostate Cancer Foundation of Australia

Funding Acknowledgements

We thank Professor Joan Massague for providing the MDA-MB-231 LM2 cell line and Dr Ross Dickins for providing the pLMP-puro-GFP construct. We thank Dr Agatha Labrinidis and Ms Yuka Harata-Lee for assistance with bioluminescence imaging and inoculation of tumour cells, respectively, Dr Peter Diamond for help with bone histological analysis and Professors Andreas Evdokiou and Shaun McColl for insightful discussions. This work was supported by fellowships from the National Breast Cancer Foundation of Australia (PAG, CPB and RLA, nos ECF-09-08 and PF-09-03) and grants from the National Health and Medical Research Council of Australia (PAG, YK-G, GJG, RLA and CNJ, nos 566871 and APP1020280), Cancer Council South Australia (GJG, PAG and YK-G) and Prostate Cancer Foundation of Australia (LAS, no. YI 0810).