Oncotarget

Research Papers:

MARCKS promotes invasion and is associated with biochemical recurrence in prostate cancer

Emma Dorris, Amanda O’Neill, Karen Hanrahan, Ann Treacy and R. William Watson _

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Oncotarget. 2017; 8:72021-72030. https://doi.org/10.18632/oncotarget.18894

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Abstract

Emma Dorris1, Amanda O’Neill1, Karen Hanrahan1, Ann Treacy2 and R. William Watson1

1UCD School of Medicine, Conway Institute for Biomedical and Biomolecular Sciences, University College Dublin, Belfield, Dublin 4, Ireland

2Pathology Department, Mater Private Hospital, Dublin 7, Ireland

Correspondence to:

R. William Watson, email: [email protected]

Keywords: prostate cancer, biochemical recurrence, MARCKS, invasion, migration

Received: January 11, 2016    Accepted: May 31, 2017    Published: June 30, 2017

ABSTRACT

Background: Overtreatment of low-grade prostate cancer is a recognised problem for clinicians and patients. However, under-treatment runs the risk of missing the opportunity for cure in those who could benefit. Identification of new biomarkers of disease progression, including metastases, is required to better stratify and appropriately treat these patients. The ability to predict if prostate cancer will recur is an important clinical question that would impact treatment options for patients. Studies in other cancers have associated MARCKS with metastasis.

Methods: Tissue microarrays of local prostatectomy samples from a cohort of biochemical recurrent and non-biochemical recurrent tumours were assayed for MARCKS protein expression. Prostate cancer cell lines were transfected with siRNA targeting MARCKS or a control and functional endpoints of migration, invasion, proliferation, viability and apoptosis were measured. Actin was visualised by fluorescent microscopy and evidence of a cadherin switch and activation of the AKT pathway were assayed.

Results: MARCKS was upregulated in biochemical recurrent patients compared to non-biochemical recurrent. Knockdown of MARCKS reduced migration and invasion of prostate cancer cells, reduced MMP9 mRNA expression, as well as decreasing cell spreading and increased cell:cell adhesion in prostate cancer cell colonies. Knockdown of MARCKS had no effect on proliferation, viability or apoptosis of the prostate cancer cells.

Conclusions: In conclusion, MARCKS promotes migration and invasion and is associated with biochemical recurrence in localised prostate cancer tumours. The mechanisms by which this occurs have yet to be fully elucidated but lack of a cadherin switch indicates it is not via epithelial-to-mesenchymal transition. Actin rearrangement indicates that MARCKS promotes invasion through regulating the architecture of the cell.


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