Molecular mechanisms underlying progesterone-enhanced breast cancer cell migration

Hui Chen Wang, Wen Sen Lee

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Progesterone (P4) was demonstrated to inhibit migration in vascular smooth muscle cells (VSMCs), but to enhance migration in T47D breast cancer cells. To investigate the mechanism responsible for this switch in P4 action, we examined the signaling pathway responsible for the P4-induced migration enhancement in breast cancer cell lines, T47D and MCF-7. Here, we demonstrated that P4 activated the cSrc/AKT signaling pathway, subsequently inducing RSK1 activation, which in turn increased phosphorylation of p27 at T198 and formation of the p27pT198-RhoA complex in the cytosol, thereby preventing RhoA degradation, and eventually enhanced migration in T47D cells. These findings were confirmed in the P4-treated MCF-7. Comparing the P4-induced molecular events in between breast cancer cells and VSMCs, we found that P4 increased p27 phosphorylation at T198 in breast cancer cells through RSK1 activation, while P4 increased p27 phosphorlation at Ser10 in VSMCs through KIS activation. P27pT198 formed the complex with RhoA and prevented RhoA degradation in T47D cells, whereas p-p27Ser10 formed the complex with RhoA and caused RhoA degradation in VSMCs. The results of this study highlight the molecular mechanism underlying P4-enhanced breast cancer cell migration, and suggest that RSK1 activation is responsible for the P4-induced migration enhancement in breast cancer cells.

Original languageEnglish
Article number31509
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Aug 11 2016

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Cell Movement
Progesterone
Breast Neoplasms
Vascular Smooth Muscle
Smooth Muscle Myocytes
Phosphorylation
Cytosol
Cell Line

ASJC Scopus subject areas

  • General

Cite this

Molecular mechanisms underlying progesterone-enhanced breast cancer cell migration. / Wang, Hui Chen; Lee, Wen Sen.

In: Scientific Reports, Vol. 6, 31509, 11.08.2016.

Research output: Contribution to journalArticle

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