AmotL2 disrupts apical–basal cell polarity and promotes tumour invasion

Mahdi Mojallal, Yujuan Zheng, Sara Hultin, Stéphane Audebert, Tanja van Harn, Per Johnsson, Claes Lenander, Nicolas Fritz, Christin Mieth, Martin Corcoran, Frédérique Lembo, Marja Hallström, Johan Hartman, Nathalie M. Mazure, Thomas Weide, Dan Grandér, Jean-Paul Borg, Per Uhlén and Lars Holmgren ()
Additional contact information
Mahdi Mojallal: Cancer Centrum Karolinska, Karolinska Institutet
Yujuan Zheng: Cancer Centrum Karolinska, Karolinska Institutet
Sara Hultin: Cancer Centrum Karolinska, Karolinska Institutet
Stéphane Audebert: Inserm U1068, CRCM
Tanja van Harn: Cancer Centrum Karolinska, Karolinska Institutet
Per Johnsson: Cancer Centrum Karolinska, Karolinska Institutet
Claes Lenander: Cancer Centrum Karolinska, Karolinska Institutet
Nicolas Fritz: Laboratory of Molecular Neurobiology, Karolinska Institutet
Christin Mieth: Max-Delbrück-Center for Molecular Medicine (MDC)
Martin Corcoran: Cancer Centrum Karolinska, Karolinska Institutet
Frédérique Lembo: Inserm U1068, CRCM
Marja Hallström: Cancer Centrum Karolinska, Karolinska Institutet
Johan Hartman: Cancer Centrum Karolinska, Karolinska Institutet
Nathalie M. Mazure: Institute for Research on Cancer and Ageing of Nice (IRCAN), UMR CNRS 7284–INSERM U1081–UNS, Université de Nice-Sophia-Antipolis
Thomas Weide: University Hospital Muenster, Albert-Schweitzer-Campus 1
Dan Grandér: Cancer Centrum Karolinska, Karolinska Institutet
Jean-Paul Borg: Inserm U1068, CRCM
Per Uhlén: Laboratory of Molecular Neurobiology, Karolinska Institutet
Lars Holmgren: Cancer Centrum Karolinska, Karolinska Institutet

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: 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.

Date: 2014
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms5557 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5557

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms5557

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().