title: A novel role for the SUMO E3 ligase PIAS1 in cancer metastasis.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada ; Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Shorafidinkhuja
authors.initials: S
authors.lastname: Dadakhujaev
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada ; McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Carolina
authors.initials: C
authors.lastname: Salazar-Arcila
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada ; Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Netherton
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada ; Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Amrita Singh
authors.initials: AS
authors.lastname: Chandhoke
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada ; McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Arvind Kumar
authors.initials: AK
authors.lastname: Singla
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada ; McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Frank R
authors.initials: FR
authors.lastname: Jirik
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada ; Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Shirin
authors.initials: S
authors.lastname: Bonni
keywords: Cancer metastasis; PIAS1; SUMO E3 ligase; three-dimensional cultures