Endoplasmic Reiculum Stress Inducers Suppress Motility and Lead to Shape Change of Normal and Tumor Human Cells in vitro

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Abstract

Endoplasmic reticulum (ER) stress and the resulting unfolded protein response (UPR) play an important role in functioning and progression of many types of tumors. In particular, ER stress can both stimulate and suppress cell motility, invasiveness, and metastasis. Contribution of ER stress induced by varying mechanisms to changes of cell motility parameters of normal and tumor cells is poorly understood. In this study, weinvestigated the different effects of ER stress inducers bortezomib, tunicamycin, and dithiothreitol (DTT) on cell motility, area, and shape of normal and tumor cells of epidermal origin, HaCaT and A431, respectively, in the presence of the agent and after its removal from the culture medium. We showed that HaCaT cell motility was suppressed by bortezomib, tunicamycin, and DTT and was restored after removal of the agent. Effects of bortezomib and DTT are accompanied by a reversible decrease in area and an increase in the form factor: HaCaT cells become rounded, with fewer protrusions. The effect of bortezomib on A431 cells leads to an irreversible decrease in motility without significant changes in area or shape; the decrease in motility after incubation of cells with tunicamycin and DTT, on the contrary, is reversible. In conclusion, ER stress inducers suppress cell motility of immortalized HaCaT keratinocytes and A431 epidermoid carcinoma cells regardless of the induction mechanism. Observed changes in cell area and shape, as well as the reversibility of these phenomena, depend on the cell type and the induction mechanism.

About the authors

I. I. Zakharov

Lomonosov Moscow State University, Faculty of Biology; Shenzhen MSU-BIT University

Email: galina22@mail.ru
Moscow, Russian Federation; Shenzhen, Guangdong Province, China

P. A. Veselova

Lomonosov Moscow State University, Faculty of Biology; Institute of Biomedical Chemistry

Email: galina22@mail.ru
Moscow, Russian Federation; Moscow, Russian Federation

M. A. Savitskaya

Lomonosov Moscow State University, Faculty of Biology

Email: galina22@mail.ru
Moscow, Russian Federation

E. A. Smirnova

Lomonosov Moscow State University, Faculty of Biology; Shenzhen MSU-BIT University

Email: galina22@mail.ru
Moscow, Russian Federation; Shenzhen, Guangdong Province, China

G. E. Onishchenko

Lomonosov Moscow State University, Faculty of Biology

Email: galina22@mail.ru
Moscow, Russian Federation

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