WW-Domain Containing Protein Roles in Breast Tumorigenesis.

Abrar Jamous,Zaidoun Salah

doi:10.3389/fonc.2018.00580

Abstract

Protein-protein interactions are key factors in executing protein function. These interactions are mediated through different protein domains or modules. An important domain found in many different types of proteins is WW domain. WW domain-containing proteins were shown to be involved in many human diseases including cancer. Some of these proteins function as either tumor suppressor genes or oncogenes, while others show dual identity. Some of these proteins act on their own and alter the function(s) of specific or multiple proteins implicated in cancer, others interact with their partners to compose WW domain modular pathway. In this review, we discuss the role of WW domain-containing proteins in breast tumorigenesis. We give examples of specific WW domain containing proteins that play roles in breast tumorigenesis and explain the mechanisms through which these proteins lead to breast cancer initiation and progression. We discuss also the possibility of using these proteins as biomarkers or therapeutic targets.

Highlights

Protein function is determined by the domains and motifs that it harbors
A careful inspection of the data presented by Watanabe et al showed the following: first, there was no normal control cells to which the expression of WWOX was compared and second, the expression of WWOX in the tested cell lines varied and there were at least 16 cell lines that showed a very low WWOX expression when compared to, for example, MCF7 cell line. These results indicate that WWOX loss in cancer is not a black and white phenomenon, but like many other tumor suppressor genes, WWOX expression is very heterogeneous in cancer samples
Since PD/PD-L1 interaction is currently targeted for cancer immunotherapy, these findings suggest that yes-associated protein (YAP)/Transcriptional coactivator with PDZ-binding motif (TAZ) might be used as a predictive factors for PD/PD-L1 based cancer immunotherapy

Summary

INTRODUCTION

Protein function is determined by the domains and motifs that it harbors. These domains can be functional domains such as the catalytic domains found in many enzymes, or structural domains that are important for protein-protein interactions or the assembly of multi-protein complexes. In this study, WWOX interaction with Breast Cancer gene (BRCA1) was shown to affect DNA DSB repair pathway choice and affects cell response to DSB inducing agents [25, 26] These findings prove that WWOX plays an important role in DDR and genomic stability, which might make it a marker for the success of DDR-targeting biological therapies. It was revealed that MicroRNA-200a promotes anoikis resistance and metastasis by targeting YAP1 in human breast cancer [88] This controversy about YAP tumor suppressor and oncogenic functions can be explained, at least in part, by the fact that YAP has different isoforms which are differentially expressed in tissues as a result of differential splicing [89]. This will help in the development of better YAP/TAZ based potential breast cancer treatments

UBIQUITIN LIGASES AND BREAST CANCER

Findings

CONCLUDING REMARKS AND FUTURE DIRECTIONS