TY  - JOUR
AB  - The therapeutic potential of Musashi (MSI) RNA-binding proteins, important stemness-associated gene expression regulators, remains insufficiently understood in breast cancer. This study identifies the interplay between MSI protein expression, stem cell characteristics, radioresistance, cell invasiveness and migration. MSI-1, MSI-2 and Notch pathway elements were investigated via quantitative polymerase chain reaction (qPCR) in 19 triple-negative breast cancer samples. Measurements were repeated in MDA-MB-231 cells after MSI-1 and -2 siRNA-mediated double knockdown, with further experiments performed after MSI silencing. Flow cytometry helped quantify expression of CD44 and leukemia inhibitory factor receptor (LIFR), changes in apoptosis and cell cycle progression. Proliferation and irradiation-induced effects were assessed using colony formation assays. Radiation-related proteins were investigated via Western blots. Finally, cell invasion assays and digital holographic microscopy for cell migration were performed. MSI proteins showed strong correlations with Notch pathway elements. MSI knockdown resulted in reduction of stem cell marker expression, cell cycle progression and proliferation, while increasing apoptosis. Cells were radiosensitized as radioresistance-conferring proteins were downregulated. However, MSI-silencing-mediated LIFR downregulation resulted in enhanced cell invasion and migration. We conclude that, while MSI knockdown results in several therapeutically desirable consequences, enhanced invasion and migration need to be counteracted before knockdown advantages can be fully exploited.
AU  - Troschel, Fabian Martin
AU  - Minte, Annemarie
AU  - Ismail, Yahia Mahmoud
AU  - Kamal, Amr
AU  - Abdullah, Mahmoud Salah
AU  - Ahmed, Sarah Hamdy
AU  - Deffner, Marie
AU  - Kemper, Björn
AU  - Kiesel, Ludwig
AU  - Eich, Hans-Theodor
AU  - Eich, Hans Theodor
AU  - Eich, Hans Theodor
AU  - Eich, Hans Theodor
AU  - Ibrahim, Sherif
AU  - Götte, Martin
AU  - Greve, Burkhard
DA  - 2020-03-21
KW  - Musashi RNA-binding proteins
KW  - breast cancer stem cells
KW  - Notch
KW  - apoptosis
KW  - proliferation
KW  - radiotherapy
KW  - EGFR
KW  - LIFR
KW  - migration
KW  - invasiveness
LA  - eng
N1  - International Journal of Molecular Sciences 21 (2020) 6, 2169, S. 1-16
N1  - Finanziert durch den Open-Access-Publikationsfonds der Westfälischen Wilhelms-Universität Münster (WWU Münster).
PY  - 2020-03-21
TI  - Knockdown of Musashi RNA Binding Proteins Decreases Radioresistance but Enhances Cell Motility and Invasion in Triple-Negative Breast Cancer
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:6-15059421641
Y2  - 2024-11-22T05:11:20
ER  -