The lipid-transfer protein Nir2 enhances epithelial-mesenchymal transition and facilitates breast cancer metastasis.

Abstract

The involvement of epithelial-mesenchymal transition (EMT) in breast cancer metastasis has been demonstrated in many studies. However, the intracellular proteins and signaling pathways that regulate EMT have not been fully identified. Here, we show that the lipid-transfer protein Nir2 (also known as PITPNM1) enhances EMT in mammary epithelial and breast cancer cells. Nir2 overexpression decreases the expression of epithelial markers and concomitantly increases the expression of mesenchymal markers, whereas silencing of Nir2 expression by small hairpin RNA (shRNA) has opposite effects. Additionally, Nir2 expression is increased during EMT and affects cell morphology, whereas Nir2 depletion attenuates growth factor-induced cell migration. These effects of Nir2 on EMT-associated processes are mainly mediated through the PI3K/AKT and the ERK1/2 pathways. Nir2 depletion also inhibits cell invasion in vitro and lung metastasis in animal models. Immunohistochemical analysis of breast cancer tissue samples reveals a correlation between high Nir2 expression and tumor grade, and Kaplan-Meier survival curves correlate Nir2 expression with poor disease outcome. These results suggest that Nir2 not only enhances EMT in vitro and breast cancer metastasis in animal models, but also contributes to breast cancer progression in human patients.

• Authors: Omer Keinan, Amir Kedan, Nancy Gavert, Michael Selitrennik, SoHui Kim, Thomas Karn, Sven Becker, Sima Lev
• Journal: Journal of cell science (J Cell Sci) Vol. 127 Issue Pt 21 Pg. 4740-9 (Nov 01 2014) ISSN: 1477-9137 [Electronic] England
• PMID: 25179602 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014. Published by The Company of Biologists Ltd.

Chemical References

• Calcium-Binding Proteins
• Eye Proteins
• Membrane Proteins
• PITPNM1 protein, human
• Pitpnm protein, mouse

Topics

• Animals
• Breast Neoplasms (genetics, metabolism, pathology)
• Calcium-Binding Proteins (genetics, metabolism)
• Cell Line, Tumor
• Epithelial-Mesenchymal Transition (genetics, physiology)
• Eye Proteins (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Membrane Proteins (genetics, metabolism)
• Mice
• Neoplasm Invasiveness (genetics)