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Background: Polarity defects are a hallmark of most carcinomas. Cells from invasive micropapillary carcinomas (IMPCs) of the breast are characterized by a striking cell polarity inversion and represent an interesting model for the analysis of polarity abnormalities. Methods: In-depth investigation of polarity proteins in 24 IMPCs and a gene expression profiling, comparing IMPC (n = 73) with invasive carcinomas of no special type (ICNST) (n = 51) have been performed. Results: IMPCs showed a profound disorganization of the investigated polarity proteins and revealed major abnormalities in their subcellular localization. Gene expression profiling experiments highlighted a number of deregulated genes in the IMPCs that have a role in apico-basal polarity, adhesion and migration. LIN7A, a Crumbs-complex polarity gene, was one of the most differentially over-expressed genes in the IMPCs. Upon LIN7A over-expression, we observed hyperproliferation, invasion and a complete absence of lumen formation, revealing strong polarity defects. Conclusion: This study therefore shows that LIN7A has a crucial role in the polarity abnormalities associated with breast carcinogenesis.
Gruel, N., Fuhrmann, L., Lodillinsky, C., Benhamo, V., Mariani, O., Cédenot, A., … Vincent-Salomon, A. (2016). LIN7A is a major determinant of cell-polarity defects in breast carcinomas. Breast Cancer Research, 18(1). https://doi.org/10.1186/s13058-016-0680-x