Oncotarget

Research Papers:

Septin remodeling is essential for the formation of cell membrane protrusions (microtentacles) in detached tumor cells

Kristine Østevold, Ana V. Meléndez, Friederike Lehmann, Gudula Schmidt, Klaus Aktories and Carsten Schwan _

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Oncotarget. 2017; 8:76686-76698. https://doi.org/10.18632/oncotarget.20805

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Abstract

Kristine Østevold1,2, Ana V. Meléndez1, Friederike Lehmann1,3,4, Gudula Schmidt1, Klaus Aktories1,5 and Carsten Schwan1

1Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty, University of Freiburg, 79104 Freiburg, Germany

2Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany

3Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, 79104 Freiburg, Germany

4Faculty of Chemistry and Pharmacy, University of Freiburg, 79104 Freiburg, Germany

5Centre for Biological Signalling Studies (BIOSS), University of Freiburg, 79104 Freiburg, Germany

Correspondence to:

Carsten Schwan, email: [email protected]

Klaus Aktories, email: [email protected]

Keywords: septin, microtentacles, microtubules, Clostridium difficile toxin, actin ADP-ribosylation

Received: June 21, 2017     Accepted: August 17, 2017     Published: September 11, 2017

ABSTRACT

Microtentacles are mostly microtubule-based cell protrusions that are formed by detached tumor cells. Here, we report that the formation of tumor cell microtentacles depends on the presence and dynamics of guanine nucleotide-binding proteins of the septin family, which are part of the cytoskeleton. In matrix-attached breast, lung, prostate and pancreas cancer cells, septins are associated with the cytosolic actin cytoskeleton. Detachment of cells causes redistribution of septins to the membrane, where microtentacle formation occurs. Forchlorfenuron, which inhibits septin functions, blocks microtentacle formation. The small GTPase Cdc42 and its effector proteins Borgs regulate septins and are essential for microtentacle formation. Dominant active and inactive Cdc42 inhibit microtentacle formation indicating that the free cycling of Cdc42 between its active and inactive state is essential for septin regulation and microtentacle formation. Cell attachment and aggregation models suggest that septins play an essential role in the metastatic behavior of tumor cells.


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