Huishan Zhao1, Tracey A Martin2, Eleri L Davies3, Fiona Ruge3, Hefen Yu4, Yuxiang Zhang4, X U Teng4, Wen G Jiang3. 1. Cardiff-China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff, U.K. Department of Biochemistry and Molecular Biology, Basic Medicine School, Cancer Institute of Capital Medical University, Beijing, P.R. China Capital Medical University-Cardiff University Joint Centre for Biomedical Research; Beijing International Cooperation Base for Science and Technology on China-UK Cancer Research, Capital Medical University, Beijing, P.R. China Beijing Key Laboratory for Cancer Invasion and Metastasis Research, Beijing, P.R. China. 2. Cardiff-China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff, U.K. martinta1@cf.ac.uk. 3. Cardiff-China Medical Research Collaborative, Cardiff University School of Medicine, Heath Park, Cardiff, U.K. 4. Department of Biochemistry and Molecular Biology, Basic Medicine School, Cancer Institute of Capital Medical University, Beijing, P.R. China Capital Medical University-Cardiff University Joint Centre for Biomedical Research; Beijing International Cooperation Base for Science and Technology on China-UK Cancer Research, Capital Medical University, Beijing, P.R. China Beijing Key Laboratory for Cancer Invasion and Metastasis Research, Beijing, P.R. China.
Abstract
BACKGROUND/AIM: The ribosomal S6 protein kinase (RSK) family is an important effector of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) that could influence tumour metastasis by phosphorylating proteins in both the nuclear and cytoplasmic compartments. Aberrant expression of RSK is evident in certain malignancies but the role played by RSK in breast cancer is still not clear. This study aimed to examine the expression of RSK in human breast cancer specimens and its role to breast cancer metastasis. MATERIALS AND METHODS: The expression of RSK1 to -3 were separately examined in human breast cancer tissues (normal, n=33; cancer, n=112) using quantitative real-time polymerase chain reaction (Q-PCR) and immunohistochemistry. Migration and adhesion of breast cancer cells treated with the RSK inhibitor SL0101 were investigated by electric cell impedance sensing (ECIS). The effect on growth and invasion of RSK1-3 was then investigated using in vitro models. RESULTS: The clinical data and immunohistochemistry revealed that expression of RSK1 and RSK3 were less in tumour tissues than normal. mRNA expression of RSK2 was negatively correlated with grade, TNM staging, and survival rate. SL0101 inhibited adhesion of the MCF-7 and MDA-231 breast cancer cell lines. SL0101 suppressed MDA-231 invasion and the alternate RSK inhibitor BRD7389 inhibited the invasion of MCF-7 and MDA-231 cells. CONCLUSION: RSK1 and 3 but not RSK2 are down-regulated in breast tumour and are associated with disease progression. RSK may be a key component in the progression and metastasis of breast cancer. Copyright
BACKGROUND/AIM: The ribosomal S6 protein kinase (RSK) family is an important effector of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) that could influence tumour metastasis by phosphorylating proteins in both the nuclear and cytoplasmic compartments. Aberrant expression of RSK is evident in certain malignancies but the role played by RSK in breast cancer is still not clear. This study aimed to examine the expression of RSK in humanbreast cancer specimens and its role to breast cancer metastasis. MATERIALS AND METHODS: The expression of RSK1 to -3 were separately examined in humanbreast cancer tissues (normal, n=33; cancer, n=112) using quantitative real-time polymerase chain reaction (Q-PCR) and immunohistochemistry. Migration and adhesion of breast cancer cells treated with the RSK inhibitor SL0101 were investigated by electric cell impedance sensing (ECIS). The effect on growth and invasion of RSK1-3 was then investigated using in vitro models. RESULTS: The clinical data and immunohistochemistry revealed that expression of RSK1 and RSK3 were less in tumour tissues than normal. mRNA expression of RSK2 was negatively correlated with grade, TNM staging, and survival rate. SL0101 inhibited adhesion of the MCF-7 and MDA-231 breast cancer cell lines. SL0101 suppressed MDA-231 invasion and the alternate RSK inhibitor BRD7389 inhibited the invasion of MCF-7 and MDA-231 cells. CONCLUSION:RSK1 and 3 but not RSK2 are down-regulated in breast tumour and are associated with disease progression. RSK may be a key component in the progression and metastasis of breast cancer. Copyright
Authors: Maryam Nakhjavani; Eric Smith; Helen M Palethorpe; Yoko Tomita; Kenny Yeo; Tim J Price; Amanda R Townsend; Jennifer E Hardingham Journal: Pharmaceuticals (Basel) Date: 2021-06-30