Abstract
BackgroundPolarity 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.MethodsIn-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.ResultsIMPCs 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.ConclusionThis study therefore shows that LIN7A has a crucial role in the polarity abnormalities associated with breast carcinogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0680-x) contains supplementary material, which is available to authorized users.
Highlights
Polarity defects are a hallmark of most carcinomas
We found that the gene encoding the polarity protein Lin-seven A (LIN7A) is upregulated in invasive micropapillary carcinoma (IMPC) and we investigated the role of its over-expression in proliferation, invasion and the loss of apico-basal polarity using in vitro and in vivo experiments
The protein associated with Lin-seven 1 (PALS1), which is part of the Crumbs complex that localizes to the apical membrane and is required for apico-basal cell polarity, was expressed in the cytoplasm in 48 % of the IMPCs
Summary
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. The mucin family protein MUC1, which is normally expressed at the apical membrane, is instead localized to the external surface of these carcinomatous cell clusters. This particular architecture has been attributed to a rotation of cell. In addition to this specific pattern, IMPC tumors are associated with a striking propensity for lymphatic invasion and a high incidence of axillary lymph node metastasis, with reported rates more than 50 % higher than those of invasive carcinomas of no special type (ICNST) [2]. The prognosis of IMPC is identical to that of ICNST [3]
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