Pin1 Plays a Key Role in the Response to Treatment and Clinical Outcome in Triple Negative Breast Cancer

Overview

Journal Ther Adv Med Oncol

Specialty Oncology

Date 2020 Mar 28

PMID 32215056

Citations 4

Authors

Catherine Knowlson

Paula Haddock

Victoria Bingham

Stephen McQuaid

Paul B Mullan

Niamh E Buckley

Affiliations

Soon will be listed here.

Abstract

Background: Triple negative breast cancer (TNBC) is the subset of breast cancer associated with the poorest outcome, and currently lacks targeted treatments. Standard of care (SoC) chemotherapy often consists of DNA damaging chemotherapies ± taxanes, with a range of responses observed. However, we currently lack biomarkers to predict this response and lack alternate treatment options.

Methods: Pin1 expression was modulated and proliferation and treatment response was studied. Pin1 expression was analysed in patient samples and correlated with clinical outcome.

Results: In this study, we have shown that the prolyl isomerase, Pin1, which is highly expressed in TNBC, plays a key role in pathogenesis of the disease. Knockdown of Pin1 in TNBC resulted in cell death while the opposite is seen in normal cells. We revealed for the first time that loss of Pin1 leads to increased sensitivity to Taxol but only in the absence of functional BRCA1. Conversely, loss of Pin1 results in decreased sensitivity to DNA-damaging agents independent of BRCA1 status. Analysis of Pin1 gene or IHC-based expression in over 200 TNBC patient samples revealed a novel role for Pin1 as a TNBC-specific biomarker, with high expression associated with improved outcome in the context of SoC chemotherapy. Preliminary data indicated this may be extended to other treatment options (e.g. Cisplatin/Parp Inhibitors) that are gaining traction for the treatment of TNBC.

Conclusions: This study highlights the important role played by Pin1 in TNBC and highlights the context-dependent functions in modulating cell growth and response to treatment.

Citing Articles

Ibulocydine Inhibits Migration and Invasion of TNBC Cells via MMP-9 Regulation.

Kwon M, Park J, Ko E, Park J, Ju E, Shin S Int J Mol Sci. 2024; 25(11).

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Pin1-Catalyzed Conformation Changes Regulate Protein Ubiquitination and Degradation.

Jeong J, Usman M, Li Y, Zhou X, Lu K Cells. 2024; 13(9.

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Cinobufacini Injection Inhibits the Proliferation of Triple-Negative Breast Cancer Through the Pin1-TAZ Signaling Pathway.

Kong L, Liu X, Yu B, Yuan Y, Zhao Q, Chen Y Front Pharmacol. 2022; 13:797873.

PMID: 35450041 PMC: 9016199. DOI: 10.3389/fphar.2022.797873.

Glucocorticoid Receptor Expression Predicts Good Outcome in response to Taxane-Free, Anthracycline-Based Therapy in Triple Negative Breast Cancer.

Elkashif A, Bingham V, Haddock P, Humphries M, McQuaid S, Mullan P J Oncol. 2020; 2020:3712825.

PMID: 32565802 PMC: 7256765. DOI: 10.1155/2020/3712825.

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