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http://purl.uniprot.org/citations/29899394http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/29899394http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/29899394http://www.w3.org/2000/01/rdf-schema#comment"

Background

Redox deregulations are ubiquitous in cancer cells. However, the role of mitochondrial redox deregulation in metastasis remains unclear. In breast cancer, upregulation of mitochondrial antiapoptotic protein G1P3 (IFI6) was associated with poor distance metastasis-free survival (DMFS). Therefore, we tested the hypothesis that G1P3-induced mitochondrial redox deregulation confers metastatic potentials in breast cancer cells.

Methods

Cell migration and invasion assays; confocal and immunofluorescence microscopy; and Illumina HumanHT-12 BeadChip to assess gene expression.

Results

Consequent to its localisation on inner-mitochondrial membrane, mtROS were higher in G1P3-expressing cells (MCF-7G1P3). G1P3-overexpressing cells migrated and invaded faster than the vector controls with increased number of filopodia and F-actin bundles (p ≤ 0.05). mtROS suppression with H2O2 scavengers and mitochondrial-specific antioxidants significantly decreased migratory structures and reversed G1P3-induced migration and invasion (p ≤ 0.05). Knocking down G1P3 decreased both migration and migratory structures in MCF-7G1P3 cells. Moreover, gene networks involved in redox regulation, metastasis and actin remodelling were upregulated in MCF-7G1P3 cells.

Conclusions

G1P3-induced mtROS have a direct role in migratory structure formation and nuclear gene expression to promote breast cancer cell metastasis. Therefore, interrupting mitochondrial functions of G1P3 may improve clinical outcomes in breast cancer patients."xsd:string
http://purl.uniprot.org/citations/29899394http://purl.org/dc/terms/identifier"doi:10.1038/s41416-018-0137-3"xsd:string
http://purl.uniprot.org/citations/29899394http://purl.org/dc/terms/identifier"doi:10.1038/s41416-018-0137-3"xsd:string
http://purl.uniprot.org/citations/29899394http://purl.uniprot.org/core/author"Davenport A."xsd:string
http://purl.uniprot.org/citations/29899394http://purl.uniprot.org/core/author"Davenport A."xsd:string
http://purl.uniprot.org/citations/29899394http://purl.uniprot.org/core/author"Kaur J."xsd:string
http://purl.uniprot.org/citations/29899394http://purl.uniprot.org/core/author"Kaur J."xsd:string
http://purl.uniprot.org/citations/29899394http://purl.uniprot.org/core/author"Chowdhury N."xsd:string
http://purl.uniprot.org/citations/29899394http://purl.uniprot.org/core/author"Chowdhury N."xsd:string
http://purl.uniprot.org/citations/29899394http://purl.uniprot.org/core/author"Cheriyath V."xsd:string
http://purl.uniprot.org/citations/29899394http://purl.uniprot.org/core/author"Cheriyath V."xsd:string
http://purl.uniprot.org/citations/29899394http://purl.uniprot.org/core/author"Gaddipati L."xsd:string
http://purl.uniprot.org/citations/29899394http://purl.uniprot.org/core/author"Gaddipati L."xsd:string
http://purl.uniprot.org/citations/29899394http://purl.uniprot.org/core/author"Khalel A."xsd:string
http://purl.uniprot.org/citations/29899394http://purl.uniprot.org/core/author"Khalel A."xsd:string
http://purl.uniprot.org/citations/29899394http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/29899394http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/29899394http://purl.uniprot.org/core/name"Br. J. Cancer"xsd:string
http://purl.uniprot.org/citations/29899394http://purl.uniprot.org/core/name"Br. J. Cancer"xsd:string
http://purl.uniprot.org/citations/29899394http://purl.uniprot.org/core/pages"52-64"xsd:string
http://purl.uniprot.org/citations/29899394http://purl.uniprot.org/core/pages"52-64"xsd:string
http://purl.uniprot.org/citations/29899394http://purl.uniprot.org/core/title"G1P3 (IFI6), a mitochondrial localised antiapoptotic protein, promotes metastatic potential of breast cancer cells through mtROS."xsd:string
http://purl.uniprot.org/citations/29899394http://purl.uniprot.org/core/title"G1P3 (IFI6), a mitochondrial localised antiapoptotic protein, promotes metastatic potential of breast cancer cells through mtROS."xsd:string