التفاصيل البيبلوغرافية
| العنوان: |
Inhibition of PDIs Downregulates Core LINC Complex Proteins, Promoting the Invasiveness of MDA-MB-231 Breast Cancer Cells in Confined Spaces In Vitro. |
| المؤلفون: |
Young, Natalie, Gui, Zizhao, Mustafa, Suleiman, Papa, Kleopatra, Jessop, Emily, Ruddell, Elizabeth, Bevington, Laura, Quinlan, Roy A., Benham, Adam M., Goldberg, Martin W., Obara, Boguslaw, Karakesisoglou, Iakowos |
| المصدر: |
Cells (2073-4409); Jun2024, Vol. 13 Issue 11, p906, 27p |
| مصطلحات موضوعية: |
NUCLEAR membranes, BREAST, CANCER cells, BREAST cancer, TRIPLE-negative breast cancer, QUATERNARY structure, NUCLEAR matrix |
| الشركة/الكيان: |
SUN Microsystems Inc. |
| مستخلص: |
Eukaryotic cells tether the nucleoskeleton to the cytoskeleton via a conserved molecular bridge, called the LINC complex. The core of the LINC complex comprises SUN-domain and KASH-domain proteins that directly associate within the nuclear envelope lumen. Intra- and inter-chain disulphide bonds, along with KASH-domain protein interactions, both contribute to the tertiary and quaternary structure of vertebrate SUN-domain proteins. The significance of these bonds and the role of PDIs (protein disulphide isomerases) in LINC complex biology remains unclear. Reducing and non-reducing SDS-PAGE analyses revealed a prevalence of SUN2 homodimers in non-tumorigenic breast epithelia MCF10A cells, but not in the invasive triple-negative breast cancer MDA-MB-231 cell line. Furthermore, super-resolution microscopy revealed SUN2 staining alterations in MCF10A, but not in MDA-MB-231 nuclei, upon reducing agent exposure. While PDIA1 levels were similar in both cell lines, pharmacological inhibition of PDI activity in MDA-MB-231 cells led to SUN-domain protein down-regulation, as well as Nesprin-2 displacement from the nucleus. This inhibition also caused changes in perinuclear cytoskeletal architecture and lamin downregulation, and increased the invasiveness of PDI-inhibited MDA-MB-231 cells in space-restrictive in vitro environments, compared to untreated cells. These results emphasise the key roles of PDIs in regulating LINC complex biology, cellular architecture, biomechanics, and invasion. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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