Distinct Roles of STAT3 and STAT5 in Breast Cancer Pathogenesis and Therapy

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A Review of the Distinct Roles of STAT3 and STAT5 in the Pathogenesis and Targeted
Therapy of Breast Cancer
by
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List of Abbreviations
STAT Signal Transducer and Activator of Transcription
STAT3 Signal Transducer and Activator of Transcription 3
STAT Signal Transducer and Activator of Transcription 5
LIF Leukemia Inhibitory Factor
HER2 Human Epidermal Growth Factor
ER Endoplasmic Reticulum

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Table of Contents
List of Abbreviations..................................................................................................................2
1.0 Introduction..........................................................................................................................4
1.1 Background..........................................................................................................................6
1.2 STATs in Cancer..................................................................................................................8
1.3 STAT3 in Breast Cancer......................................................................................................8
1.4 STAT5 in Breast Cancer......................................................................................................8
1.5 Co-activation of STAT5 and STAT3 in Breast Cancer.......................................................9
2.0 Method.................................................................................................................................9
3.0 Discussion..........................................................................................................................12
References................................................................................................................................14
1.0 Introduction
The research paper by Walker, Xiang, and Frank (2014) was evaluated and analysed for the
purpose of developing a diagnostic and prognostic tool for breast cancer. The two primary
transcription factors used as diagnostic tool against breast cancer are the transducer and
activator of transcription (STAT5 and STAT3). These two prime transcription factors were
primarily used due to breast cancer cells containing an improper activation of transcription
factor involved in the development of mammary cell. Consequently the research article is
demonstrating that a prime transcription factor that possesses a significant effect in increasing
the development of mammary cell than a diagnostic could be formed for breast cancer.

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Signal transducers and activators of transcription (STATs) are latent transcription factors that
become activated after tyrosine phosphorylation by receptor and non-receptor tyrosine
kinases. After phosphorylation, the STATs become activated, shift to the nucleus, and bind to
similar STAT DNA binding places, in which they modify transcription of major target genes
convoluted in most of the cellular processes. STATs are often irrationally active in cancer:
STAT5 and STAT3 are usually activated constitutively in breast cancer, in contrast to the
transient activation which takes place physiologically (Banerjee and Resat, 2016; Walker et
al., 2009). STAT3 and STAT5 are two closely members of the STATs family that have
separate functions in the development of the mammary glands, and have also been found to
be activated in breast cancer (Brantley and Benveniste, 2008). The key steps of the signalling
pathways of the JAK-STAT is shown below. The signalling pathway comprises of three
primary proteins: STATS, JAKs, and cell-surface receptors.
Signalling Pathways
Source: (Liongue et al., 2012)
Several studies have been conducted on the relationship between transcriptional factors and
breast cancer. The first initial research developed for signal transcription factors in mammary
cell was published by Clarkson et al. (2006) and countless other scientists continued the