Research Papers:

Differential tumor biological role of the tumor suppressor KAI1 and its splice variant in human breast cancer cells

Julia Miller, Tobias F. Dreyer, Anne Benge, Eva-Kathrin Sinner, Christine Heinrich, Anke Benge, Eva Gross, Sarah Preis, Jan Rother, Anthony Roberts, Gabriele Nelles, Tzenka Miteva and Ute Reuning _

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Oncotarget. 2018; 9:6369-6390. https://doi.org/10.18632/oncotarget.23968

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Julia Miller1, Tobias F. Dreyer1, Anne Sophie Bächer1, Eva-Kathrin Sinner2, Christine Heinrich1, Anke Benge1, Eva Gross1, Sarah Preis1, Jan Rother3, Anthony Roberts3, Gabriele Nelles3, Tzenka Miteva3 and Ute Reuning1

1Department for Obstetrics & Gynecology, Technical University of Munich, D-81675 Munich, Germany

2BOKU, University of Natural Resources and Life Sciences, 1180 Vienna, Austria

3Materials Science Laboratory, Sony Europe Ltd ZN Deutschland, D-70327 Stuttgart, Germany

Correspondence to:

Ute Reuning, email: [email protected]

Tzenka Miteva, email: [email protected]

Keywords: tumor suppressor KAI1 (CD82); integrin avβ3; breast cancer; cell proliferation/adhesion/migration; cell motion vector analysis

Received: April 28, 2017    Accepted: December 23, 2017    Published: January 05, 2018


The tetraspanin and tumor suppressor KAI1 is downregulated or lost in many cancers which correlates with poor prognosis. KAI1 acts via physical/functional crosstalk with other membrane receptors. Also, a splice variant of KAI1 (KAI1-SP) has been identified indicative of poor prognosis. We here characterized differential effects of the two KAI1 variants on tumor biological events involving integrin (αvβ3) and/or epidermal growth factor receptor (EGF-R). In MDA-MB-231 and -435 breast cancer cells, differential effects were documented on the expression levels of the tumor biologically relevant integrin αvβ3 which colocalized with KAI1-WT but not with KAI1-SP. Cellular motility was assessed by video image processing, including motion detection and vector analysis for the quantification and visualization of cell motion parameters. In MDA-MB-231 cells, KAI1-SP provoked a quicker wound gap closure and higher closure rates than KAI1-WT, also reflected by different velocities and average motion amplitudes of singular cells. KAI1-SP induced highest cell motion adjacent to the wound gap borders, whereas in MDA-MB-435 cells a comparable induction of both KAI1 variants was noticed. Moreover, while KAI1-WT reduced cell growth, KAI1-SP significantly increased it going along with a pronounced EGF-R upregulation. KAI1-SP-induced cell migration and proliferation was accompanied by the activation of the focal adhesion and Src kinase. Our findings suggest that splicing of KAI1 does not only abrogate its tumor suppressive functions, but even more, promotes tumor biological effects in favor of cancer progression and metastasis.

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