Septin oligomerization regulates persistent expression of ErbB2/HER2 in gastric cancer cells.

Septin oligomerization regulates persistent expression of ErbB2/HER2 in gastric cancer cells. Biochem J. 2016 Apr 5; Authors: Marcus EA, Tokhtaeva E, Turdikulova S, Capri J, Whitelegge JP, Scott DR, Sachs G, Berditchevski F, Vagin O Abstract Septins are a family of cytoskeletal GTP-binding proteins that assemble into membrane-associated hetero-oligomers and organize scaffolds for recruitment of cytosolic proteins or stabilization of membrane proteins. Septins have been implicated in a diverse range of cancers, including gastric cancer, but the underlying mechanisms remain unclear. The hypothesis tested here is that septins contribute to cancer by stabilizing the receptor tyrosine kinase ErbB2, an important target for cancer treatment. Septins and ErbB2 were highly over-expressed in gastric cancer cells. Immunoprecipitation followed by mass-spectrometry analysis identified ErbB2 as a septin-interacting protein. Knockdown of septin-2 or cell exposure to forchlorfenuron (FCF), a well-established inhibitor of septin oligomerization, decreased surface and total levels of ErbB2. These treatments had no effect on EGFR, emphasizing the specificity and functionality of the septin-ErbB2 interaction. The level of ubiquitylated ErbB2 at the plasma membrane was elevated in cells treated with FCF, which was accompanied by a decrease in co-localization of ErbB2 with septins at the membrane.  Cathepsin B inhibitor, but not bafilomycin or lactacys...
Source: The Biochemical Journal - Category: Biochemistry Authors: Tags: Biochem J Source Type: research