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The Clinical Implications of RSK1-3 in Human Breast Cancer

Huishan Zhao1, Tracey A Martin2, Eleri L Davies3

  • 1Cardiff-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.

Anticancer Research
|March 16, 2016
PubMed
Abstract

Insights

Ribosomal S6 protein kinase (RSK) family members RSK1 and RSK3 are down-regulated in breast tumors, impacting disease progression. RSK inhibition suppresses breast cancer cell adhesion and invasion, suggesting RSK is crucial for metastasis.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • The ribosomal S6 protein kinase (RSK) family, a key effector of ERK/MAPK signaling, influences tumor metastasis through protein phosphorylation.
  • Aberrant RSK expression is observed in malignancies, but its specific role in breast cancer remains unclear.

Purpose of the Study:

  • To investigate the expression of RSK1-3 in human breast cancer specimens.
  • To determine the role of RSK in breast cancer metastasis and cellular processes like adhesion and invasion.

Main Methods:

  • Quantitative real-time PCR (Q-PCR) and immunohistochemistry were used to assess RSK1-3 expression in 112 breast cancer tissues and 33 normal tissues.
  • Breast cancer cell lines (MCF-7 and MDA-231) were treated with RSK inhibitors (SL0101, BRD7389) to evaluate effects on migration, adhesion, and invasion using electric cell impedance sensing (ECIS) and in vitro models.

Main Results:

  • RSK1 and RSK3 expression were significantly lower in tumor tissues compared to normal tissues.
  • RSK2 mRNA expression negatively correlated with tumor grade, TNM stage, and patient survival rate.
  • RSK inhibition by SL0101 reduced adhesion in MCF-7 and MDA-231 cells and suppressed MDA-231 invasion. BRD7389 inhibited invasion in both cell lines.

Conclusions:

  • RSK1 and RSK3 are downregulated in breast tumors and linked to disease progression.
  • RSK signaling plays a critical role in breast cancer progression and metastasis.
  • Targeting RSK may offer a therapeutic strategy for breast cancer treatment.
Keywords:
Metastasis suppressor geneRSKSL0101adhesionbreast tumourimmunohistochemistryinvasion

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