HMGB1 and its role in breast cancer progression and malignancy

Abstract

HMGBl is an abundant and ubiquitously expressed non-histone nuclear protein. HMGB1 is a nuclear architectural factor, but can also be found in the extracellular environment. Necrotic cells, but not apoptotic, passively release HMGBl in the extracellular environment, whereas specific cell types, such as macrophages, actively secrete HMGB1. In the extracellular milieu HMGB1 works as a cytokine and a signal of tissue damage, stimulating cell migration by an NF-KB-dependent mechanism, cell proliferation and differentiation. HMGBl is over-expressed in several types of tumors and plays a role in cancer progression and metastasis, when present in the tumor microenvironment. Moreover HMGBl over-expression protects cells from different apoptotic sdmuli and is associated to expression of genes linked to metastasis. Analyzing a panel of human breast cancer biopsies, we found almost universal HMGB1 overexpression in tumor cells, whereas HMGBl cytoplasmic relocation appears to be linked to lymph node invasion.EThOS - Electronic Theses Online ServiceGBUnited Kingdo