RSK1 promotes murine breast cancer growth and metastasis

Dominika Czaplińska , Monika Górska , Kamil Mieczkowski , Grażyna Peszyńska-Sularz , Anna Żaczek , Hanna M. Romanska , Rafał Sądej

Abstract

Introduction. Triple-negative breast cancer (TNBC), representing over 15% of all breast cancers, has a poorer prognosis than other subtypes. There is no effective targeted treatment available for the TNBC sufferers. Ribosomal S6 kinases (RSKs) have been previously proposed as drug targets for TNBC based on observations that 85% of these tumors express activated RSKs. Materials and methods. Herein we examined an involvement of RSK1 (p90 ribosomal S6 kinase 1) in a regulation of TNBC growth and metastatic spread in an animal model, which closely imitates human disease. Mice were inoculated into mammary fat pad with 4T1 cells or their RSK1-depleted variant. We examined tumor growth and formation of pulmonary metastasis. Boyden chamber, wound healing and soft agarose assays were performed to evaluate cells invasion, migration and anchorage-independent growth. Results. We found that RSK1 promoted tumor growth and metastasis in vivo. After 35 days all animals inoculated with control cells developed tumors while in the group injected with RSK1-negative cells, there were 75% tumor-bearing mice. Average tumor mass was estimated as 1.16 g and 0.37 g for RSK1-positive vs. -negative samples, respectively (p < 0.0001). Quantification of the macroscopic pulmonary metastases indicated that mice with RSK1-negative tumors developed approximately 85% less metastatic foci on the lung surface (p < 0.001). This has been supported by in vitro data presenting that RSK1 promoted anchorage-independent cell growth and migration. Moreover, RSK1 knock-down corresponded with decreased expression of cell cycle regulating proteins, i.e. cyclin D3, CDK6 and CDK4. Conclusions. We provide evidence that RSK1 supports tumor growth and metastatic spread in vivo as well as in vitro migration and survival in non-adherent conditions. Further studies of RSK1 involvement in TNBC progression may substantiate our findings, laying the foundations for development of anti-RSK1-based therapeutic strategies in the management of patients with TNBC. (Folia Histochemica et Cytobiologica 2018, Vol. 56, No. 1, 11–20)
Author Dominika Czaplińska (IFB)
Dominika Czaplińska,,
- Intercollegiate Faculty of Biotechnology UG
, Monika Górska (IFB)
Monika Górska,,
- Intercollegiate Faculty of Biotechnology UG
, Kamil Mieczkowski (IFB)
Kamil Mieczkowski,,
- Intercollegiate Faculty of Biotechnology UG
, Grażyna Peszyńska-Sularz
Grażyna Peszyńska-Sularz,,
-
, Anna Żaczek (IFB / DMedB)
Anna Żaczek,,
- Department of Medical Biotechnology
, Hanna M. Romanska
Hanna M. Romanska,,
-
, Rafał Sądej (IFB / DMedB)
Rafał Sądej,,
- Department of Medical Biotechnology
Journal seriesFolia Histochemica et Cytobiologica, ISSN 0239-8508, (A 15 pkt)
Issue year2018
Vol56
No1
Pages11-20
Publication size in sheets0.5
Keywords in EnglishRSK1 knock-down, triple-negative breast cancer, metastasis, animal model, in vitro, cell cycle regulation
DOIDOI:10.5603/FHC.a2018.0001
URL https://journals.viamedica.pl/folia_histochemica_cytobiologica/article/download/FHC.a2018.0001/43280
Languageen angielski
LicenseJournal (articles only); published final; Other open licence; with publication
Score (nominal)15
ScoreMinisterial score = 15.0, 30-05-2018, ArticleFromJournal
Ministerial score (2013-2016) = 15.0, 30-05-2018, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 1.389 (2) - 2016=1.3 (5)
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