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The function of p97/Valosin-containing protein (VCP) and small VCP-interacting protein (SVIP) in invasion and migration of pancreatic cancer cells

EBRU ALİMOĞULLARI, SEVİL ÇAYLI

Turkish Journal of Medical Sciences · 2024-10-18 · 54 (5) · 1154-1164

DOI: 10.55730/1300-0144.5894 ↗
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Rezumat

Background/aim: Misfolded proteins are eliminated by a process known as Endoplasmic reticulum-associated protein degradation (ERAD). ERAD has an impact on variety of illnesses, such as diabetes, cystic fibrosis, cancer, and neurological conditions. We concentrated on p97/Valosin-containing protein (VCP) and small VCP-interacting protein (SVIP) despite there being many proteins involved in ERAD. The existence and function of SVIP and p97/VCP in various types of pancreatic cancer have not yet been investigated. The study's objectives are to examine the expressions of SVIP and p97/VCP in two pancreatic cancer types and to show whether these proteins aid in the invasion and migration of pancreatic cancer cells.Materials and methods: In this work, MIA PaCa-2 and PANC-1 human cell lines were examined. Immunohistochemistry and immunofluorescence were performed to detect the cellular localization and presence of p97/VCP and SVIP in pancreatic cancer cells. Following p97/VCP siRNA and SVIP siRNA transfection of the cells, protein expressions were assessed using Western blot analysis. The effects of this suppression on cell invasion and migration were determined using the xCELLigence real-time analysis system (RTAC).Results: In the nucleus and cytoplasm of MIA PaCa-2 and PANC-1 cells, p97/VCP and SVIP immunoexpressions were seen. The decrease in protein expressions of p97/VCPsi and SVIPsi was significant in pancreatic cells compared to the controlsi. p97/VCP siRNA transfection reduced invasion and migration of MIA PaCa-2 and PANC-1 cells. In addition, SVIP siRNA suppression resulted in increasing invasion and migration ability of both cells. This study also demonstrated, for the first time, SVIP expression in MIA PaCa-2 and PANC-1 cells.Conclusion: Overall, our findings show the differential expression and function of p97/VCP and SVIP in pancreas ductal adenocarcinoma cells. The potential of pancreatic cancer cells to migrate and invade altered when the two cell lines were transfected with p97/VCPsi and SVIPsi.

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