Increased expression of plakoglobin is associated with upregulated MAPK and PI3K/AKT signalling pathways in early resectable pancreatic ductal adenocarcinoma

Nweke,Ekene; Ntwasa,Monde; Brand,Martin; Devar,John; Smith,Martin; Candy,Geoffrey

doi:10.3892/ol.2020.11473

Increased expression of plakoglobin is associated with upregulated MAPK and PI3K/AKT signalling pathways in early resectable pancreatic ductal adenocarcinoma

Authors:
- Ekene Nweke
- Monde Ntwasa
- Martin Brand
- John Devar
- Martin Smith
- Geoffrey Candy
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Affiliations: Department of Surgery, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, Gauteng 2193, Republic of South Africa, Department of Life and Consumer Sciences, University of South Africa, Johannesburg, Gauteng 1710, Republic of South Africa, School of Physiology, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, Gauteng 2193, Republic of South Africa
Published online on: March 23, 2020 https://doi.org/10.3892/ol.2020.11473
Pages: 4133-4141
Copyright: © Nweke et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancer types, and it is associated with a 5‑year survival rate of <10% due to limited early detection methods and ineffective therapeutic options. Thus, an improved understanding of the mechanisms involved in the early stages of PDAC tumorigenesis is crucial in order to identify potential novel diagnostic and therapeutic targets. The most common signalling aberrations in PDAC occur in the Wnt/Notch signalling pathway, as well as within the epidermal growth factor receptor (EGFR) pathway and its associated ligands, EGF and transforming growth factor‑β. In addition, the RAS family of oncogenes, which act downstream of EGFR, are found mutated in most pancreatic cancer samples. Plakoglobin, a component of the EGFR signalling pathway, serves an important role in normal cell adhesion; however, its role in PDAC is largely unknown. The present study used transcriptome sequencing and focussed proteome microarrays to identify dysregulated genes and proteins in PDAC. The presence of upregulated plakoglobin expression levels was identified as a distinguishing feature between the PDAC microenvironment and normal pancreatic tissue. Furthermore, plakoglobin was demonstrated to be associated with the differential upregulation of the PI3K/AKT and MAPK signalling pathways in the tumour microenvironment, which suggested that it may serve an important role in PDAC tumourigenesis.

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