OncoTargets and Therapy (Nov 2017)
The crossroads of breast cancer progression: insights into the modulation of major signaling pathways
Abstract
Fernando J Velloso,1,* Arthur FR Bianco,2,* Jessica O Farias,3 Nadia EC Torres,4 Pault YM Ferruzo,3 Valesca Anschau,5 Henrique C Jesus-Ferreira,1 Ted Hung-Tse Chang,6 Mari Cleide Sogayar,1 Luiz F Zerbini,6 Ricardo G Correa7 1Cell and Molecular Therapy Center (NUCEL-NETCEM), School of Medicine, 2Department of Pharmacology, Biomedical Sciences Institute, 3Department of Biochemistry, Institute of Chemistry, 4Departament of Immunology, Biomedical Sciences Institute, 5Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo, São Paulo, Brazil; 6Cancer Genomics Group, International Center for Genetic Engineering and Biotechnology (ICGEB), Cape Town, South Africa; 7Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA *These authors contributed equally to this work Abstract: Cancer is the disease with highest public health impact in developed countries. Particularly, breast cancer has the highest incidence in women worldwide and the fifth highest mortality in the globe, imposing a significant social and economic burden to society. The disease has a complex heterogeneous etiology, being associated with several risk factors that range from lifestyle to age and family history. Breast cancer is usually classified according to the site of tumor occurrence and gene expression profiling. Although mutations in a few key genes, such as BRCA1 and BRCA2, are associated with high breast cancer risk, the large majority of breast cancer cases are related to mutated genes of low penetrance, which are frequently altered in the whole population. Therefore, understanding the molecular basis of breast cancer, including the several deregulated genes and related pathways linked to this pathology, is essential to ensure advances in early tumor detection and prevention. In this review, we outline key cellular pathways whose deregulation has been associated with breast cancer, leading to alterations in cell proliferation, apoptosis, and the delicate hormonal balance of breast tissue cells. Therefore, here we describe some potential breast cancer-related nodes and signaling concepts linked to the disease, which can be positively translated into novel therapeutic approaches and predictive biomarkers. Keywords: breast cancer, estrogen receptor, PI3K, MAPK, JAK/STAT, Wnt, TGFβ, NFκB
