A Novel Role for the SUMO E3 Ligase PIAS1 in Cancer Metastasis

Overview

Journal Oncoscience

Specialty Oncology

Date 2015 Jan 17

PMID 25594015

Citations 24

Authors

Shorafidinkhuja Dadakhujaev

Carolina Salazar-Arcila

Stuart J Netherton

Amrita Singh Chandhoke

Arvind Kumar Singla

Frank R Jirik

Shirin Bonni

Affiliations

Soon will be listed here.

Abstract

Tumor metastasis contributes to the grave morbidity and mortality of cancer, but the mechanisms underlying tumor cell invasiveness and metastasis remain incompletely understood. Here, we report that expression of the SUMO E3 ligase PIAS1 suppresses TGFβ-induced activation of the matrix metalloproteinase MMP2 in human breast cancer cells. We also find that knockdown of endogenous PIAS1 or inhibition of its SUMO E3 ligase activity stimulates the ability of TGFβ to induce an aggressive phenotype in three-dimensional breast cancer cell organoids. Importantly, inhibition of the SUMO E3-ligase activity of PIAS1 in breast cancer cells promotes metastases in mice in vivo. Collectively, our findings define a novel and critical role for the SUMO E3 ligase PIAS1 in the regulation of the invasive and metastatic potential of malignant breast cancer cells. These findings advance our understanding of cancer invasiveness and metastasis with potential implications for the development of biomarkers and therapies in breast cancer.

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