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Src tyrosyl phosphorylates cortactin in response to prolactin
Alan Hammer1, Sneha Laghate1, Maria Diakonova1
1The Department of Biological Sciences, University of Toledo, 2801 W. Bancroft Street, Toledo, OH, 43606-3390, USA.
Biochemical and Biophysical Research Communications
|June 6, 2015
Summary
Prolactin (PRL) drives breast cancer invasion through JAK2/PAK1 and a novel Src-dependent pathway activating cortactin. This highlights dual mechanisms in PRL-induced metastasis.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Prolactin (PRL) is a hormone implicated in breast cancer progression, particularly cell invasion and metastasis.
- PRL signaling pathways often involve non-receptor tyrosine kinases like JAK2 and Src.
- Previous work linked prolactin-induced breast cancer cell invasion to the JAK2/PAK1 pathway.
Purpose of the Study:
- To investigate the role of the actin-binding protein cortactin in prolactin-mediated breast cancer cell invasion.
- To elucidate the specific signaling pathways, including JAK2 and Src kinases, involved in prolactin's effects on invasion and cortactin activation.
Main Methods:
- Comparative invasion assays using TMX2-28 and T47D breast cancer cell lines in response to prolactin.
- Analysis of cortactin tyrosyl phosphorylation following prolactin stimulation.
- Kinase inhibition studies to determine the roles of JAK2 and Src in prolactin-mediated invasion and cortactin phosphorylation.
Main Results:
- Prolactin significantly increased invasion in TMX2-28 cells compared to T47D cells.
- Prolactin induced time- and dose-dependent tyrosyl phosphorylation of cortactin in TMX2-28 cells, mediated by Src, not JAK2.
- Maximal prolactin-induced invasion in TMX2-28 cells required both Src and JAK2, while T47D cell invasion was JAK2-dependent only.
Conclusions:
- Prolactin stimulates breast cancer cell invasion through at least two distinct pathways.
- One pathway involves JAK2/PAK1, previously identified.
- A second, novel pathway involves Src-dependent activation and tyrosyl phosphorylation of cortactin, contributing to invasion.
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