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AmotL2 disrupts apical-basal cell polarity and promotes tumour invasion

Item Type:Article
Title:AmotL2 disrupts apical-basal cell polarity and promotes tumour invasion
Creators Name:Mojallal, M., Zheng, Y., Hultin, S., Audebert, S., van Harn, T., Johnsson, P., Lenander, C., Fritz, N., Mieth, C., Corcoran, M., Lembo, F., Hallstroem, M., Hartman, J., Mazure, N.M., Weide, T., Grander, D., Borg, J.P., Uhlen, P. and Holmgren, L.
Abstract:The establishment and maintenance of apical-basal cell polarity is essential for the functionality of glandular epithelia. Cell polarity is often lost in advanced tumours correlating with acquisition of invasive and malignant properties. Despite extensive knowledge regarding the formation and maintenance of polarity, the mechanisms that deregulate polarity in metastasizing cells remain to be fully characterized. Here we show that AmotL2 expression correlates with loss of tissue architecture in tumours from human breast and colon cancer patients. We further show that hypoxic stress results in activation of c-Fos-dependent expression of AmotL2 leading to loss of polarity. c-Fos/hypoxia-induced p60 AmotL2 interacts with the Crb3 and Par3 polarity complexes retaining them in large vesicles and preventing them from reaching the apical membrane. The resulting loss of polarity potentiates the response to invasive cues in vitro and in vivo in mice. These data provide a molecular mechanism how hypoxic stress deregulates cell polarity during tumour progression.
Keywords:Anoxia, Breast Neoplasms, Caco-2 Cells, Carrier Proteins, Cell Cycle Proteins, Cell Polarity, Colonic Neoplasms, HeLa Cells, Human Mammary Glands, Lymph Nodes, Membrane Glycoproteins, Membrane Proteins, Neoplasm Invasiveness, Neoplasm Staging, Neoplasm Transplantation, Neoplastic Gene Expression Regulation, Proto-Oncogene Proteins c-fos, SCID Mice, Signal Transduction, Transport Vesicles, Animals, Mice
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:4557
Date:1 August 2014
Official Publication:https://doi.org/10.1038/ncomms5557
PubMed:View item in PubMed

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