Cancers, Vol. 11, Pages 556: Altered Expression and Localization of Tumor Suppressive E3 Ubiquitin Ligase SMURF2 in Human Prostate and Breast Cancer

Cancers, Vol. 11, Pages 556: Altered Expression and Localization of Tumor Suppressive E3 Ubiquitin Ligase SMURF2 in Human Prostate and Breast Cancer Cancers doi: 10.3390/cancers11040556 Authors: Andrea Emanuelli Dhanoop Manikoth Ayyathan Praveen Koganti Pooja Anil Shah Liat Apel-Sarid Biagio Paolini Rajesh Detroja Milana Frenkel-Morgenstern Michael Blank SMURF2, an E3 ubiquitin ligase and suggested tumor suppressor, operates in normal cells to prevent genomic instability and carcinogenesis. However, the mechanisms underlying SMURF2 inactivation in human malignancies remain elusive, as SMURF2 is rarely found mutated or deleted in cancers. We hypothesized that SMURF2 might have a distinct molecular biodistribution in cancer versus normal cells and tissues. The expression and localization of SMURF2 were analyzed in 666 human normal and cancer tissues, with primary focus on prostate and breast tumors. These investigations were accompanied by SMURF2 gene expression analyses, subcellular fractionation and biochemical studies, including SMURF2’s interactome analysis. We found that while in normal cells and tissues SMURF2 has a predominantly nuclear localization, in prostate and aggressive breast carcinomas SMURF2 shows a significantly increased cytoplasmic sequestration, associated with the disease progression. Mechanistic studies showed that the nuclear export machinery was not involved in cytoplasmic accumulation of SMURF2, while uncovered tha...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research