Protein Phosphatase 2A (PP2A) is a major serine/threonine phosphatase in cells. It consists of a catalytic subunit (C), a structural subunit (A), and a regulatory/variable B-type subunit. PP2A has a critical role to play in homeostasis where its predominant function is as a phosphatase that regulates the major cell signaling pathways in cells. Changes in the assembly, activity and substrate specificity of the PP2A holoenzyme have a direct role in disease and are a major contributor to the maintenance of the transformed phenotype in cancer. We have learned a lot about how PP2A functions from specific mutations that disrupt the core assembly of PP2A and from viral proteins that target PP2A and inhibit its effect as a phosphatase. This prompted various studies revealing that restoration of PP2A activity benefits some cancer patients. However, our understanding of the mechanism of action of this is limited because of the complex nature of PP2A holoenzyme assembly and because it acts through a wide variety of signaling pathways. Information on PP2A is also conflicting as there are situations whereby inactivation of PP2A induces apoptosis in many cancer cells. In this review we discuss this relationship and we also address many of the pertinent and topical questions that relate to novel therapeutic strategies aimed at altering PP2A activity.

Signalling proteins are intrinsic to all biological processes and interact with each other in tightly regulated and orchestrated signalling complexes and pathways. Characterization of protein binding can help to elucidate protein function within signalling pathways. This information is vital for researchers to gain a more comprehensive knowledge of cellular networks which can then be used to develop new therapeutic strategies for disease. However, studying protein–protein interactions (PPIs) can be challenging as the interactions can be extremely transient downstream of specific environmental cues. There are many powerful techniques currently available to identify and confirm PPIs. Choosing the most appropriate range of techniques merits serious consideration. The aim of this review is to provide a starting point for researchers embarking on a PPI study. We provide an overview and point of reference for some of the many methods available to identify interactions from in silico analysis and large scale screening tools through to the methods used to validate potential PPIs. We discuss the advantages and disadvantages of each method and we also provide a workflow chart to highlight the main experimental questions to consider when planning cell lysis to maximize experimental success.

Conventional therapies for cancer such as chemotherapy and radiotherapy remain a mainstay in treatment, but in many cases a targeted approach is lacking, and patients can be vulnerable to drug resistance. In recent years, novel concepts have been emerging to improve the traditional therapeutic options in cancers with poor survival outcomes. New therapeutic strategies involving areas like energy metabolism and extracellular vesicles along with advances in immunotherapy and nanotechnology are driving the next generation of cancer treatments. The development of fields such as theranostics in nanomedicine is also opening new doors for targeted drug delivery and nano-imaging. Here we discuss the use of innovative technologies presented at the Irish Association for Cancer Research (IACR) Annual Meeting, highlighting examples of where new approaches may lead to promising new treatment options for a range of cancer types.

Background: Metastasis is the number one cause of death in breast cancer patients. Understanding how and why cancer cells migrate is of significant clinical interest. Accumulating evidence suggests that the spread of breast cancer is influenced by the extracellular matrix (ECM). The ECM refers to the area around the tumour containing various proteins and cells; influencing tumour structure and behaviour. Methods: We examined a panel of 40 genes that code for several categories of proteins that regulate the composition of the ECM. We selected this panel as they are known to be active at the leading edge of the cell or secreted into the ECM. We used STRING an online tool to examine the relationship between the genes based on the experimental determination of protein homology and protein co-expression. Results: Using quantitative real-time polymerase chain reaction (qRT-PCR), we examined gene dysregulation in different cell lines that represent various models of breast cancers. Cells were cultured in 2D and 3D models. Models will be used to validate our approach on matched tissue reflecting subtypes of breast cancer patients. By investigating how the cell interacts with its environment we aim to identify the first genetic changes happening in the cell as it becomes invasive. Conclusions: This work could provide opportunity to generate a novel gene signature that may be used to predict invasive cancers, the primary step in cancer metastasis. It may also provide information on the design of novel treatment therapies for patients with metastatic cancers.