TAp73 represses NF-κB-mediated recruitment of tumor-associated macrophages in breast cancer.

Infiltration of tumor-promoting immune cells is a strong driver of tumor progression. Especially the accumulation of macrophages in the tumor microenvironment is known to facilitate tumor growth and to correlate with poor prognosis in many tumor types. TAp73, a member of the p53/p63/p73 family, acts as a tumor suppressor and has been shown to suppress tumor angiogenesis.

ΔNp73 enhances HIF-1α protein stability through repression of the ECV complex.

Cellular responses to low oxygen conditions are mainly regulated by the Hypoxia-inducible factors (HIFs). Induction of HIF-1α in tumor cells activates the angiogenic switch and allows for metabolic adaptations. HIF-1α protein levels are tightly regulated through ubiquitin-mediated proteosomal degradation; however, high levels of HIF-1α is a common feature in many solid tumors and is thought to enhance cancer cell proliferation, migration, and survival.

ΔNp73 regulates the expression of the multidrug-resistance genes ABCB1 and ABCB5 in breast cancer and melanoma cells - a short report.

Purpose: Multidrug resistance (MDR) is a major cause of treatment failure. In cancer cells, MDR is often caused by an increased efflux of therapeutic drugs mediated by an up-regulation of ATP binding cassette (ABC) transporters. It has previously been shown that oncogenic ΔNp73 plays an important role in chemo-resistance.

TAp73 suppresses tumor angiogenesis through repression of proangiogenic cytokines and HIF-1α activity.

The p53-family member TAp73 is known to function as a tumor suppressor and regulates genomic integrity, cellular proliferation, and apoptosis; however, its role in tumor angiogenesis is poorly understood. Here we demonstrate that TAp73 regulates tumor angiogenesis through repression of proangiogenic and proinflammatory cytokines. Importantly, loss of TAp73 results in highly vascularized tumors, as well as an increase in vessel permeability resulting from disruption of vascular endothelial-cadherin junctions between endothelial cells.