title: Inositol 1, 4, 5-trisphosphate-dependent nuclear calcium signals regulate angiogenesis and cell motility in triple negative breast cancer.
abstract: Increases in nuclear calcium concentration generate specific biological outcomes that differ from those resulting from increased cytoplasmic calcium. Nuclear calcium effects on tumor cell proliferation are widely appreciated; nevertheless, its involvement in other steps of tumor progression is not well understood. Therefore, we evaluated whether nuclear calcium is essential in other additional stages of tumor progression, including key steps associated with the formation of the primary tumor or with the metastatic cascade. We found that nuclear calcium buffering impaired 4T1 triple negative breast cancer growth not just by decreasing tumor cell proliferation, but also by enhancing tumor necrosis. Moreover, nuclear calcium regulates tumor angiogenesis through a mechanism that involves the upregulation of the anti-angiogenic C-X-C motif chemokine 10 (CXCL10-IP10). In addition, nuclear calcium buffering regulates breast tumor cell motility, culminating in less cell invasion, likely due to enhanced vinculin expression, a focal adhesion structural protein. Together, our results show that nuclear calcium is essential for triple breast cancer angiogenesis and cell migration and can be considered as a promising strategic target for triple negative breast cancer therapy.
authors.affiliation: Department of Molecular Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil.|Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Erika
authors.initials: E
authors.lastname: Guimarães
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Machado
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.|Brazilian National Laboratory for Biosciences, Center for Research in Energy and Materials, Campinas, Brazil.
authors.forename: Matheus de Castro
authors.initials: MC
authors.lastname: Fonseca
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Andressa
authors.initials: A
authors.lastname: França
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Clarissa
authors.initials: C
authors.lastname: Carvalho
authors.affiliation: Department of Pharmacology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Ana Cândida
authors.initials: AC
authors.lastname: Araújo E Silva
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Brígida
authors.initials: B
authors.lastname: Almeida
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Puebla
authors.initials: P
authors.lastname: Cassini
authors.affiliation: Department of Physics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Hissa
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Drumond
authors.affiliation: Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Carlos
authors.initials: C
authors.lastname: Gonçalves
authors.affiliation: Genomics Sciences and Biotechnology of Universidade Católica de Brasília, Brasília, Brazil.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Fernandes
authors.affiliation: Department of Pathological Anatomy, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Marina
authors.initials: M
authors.lastname: De Brot
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Márcio
authors.initials: M
authors.lastname: Moraes
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Lucíola
authors.initials: L
authors.lastname: Barcelos
authors.affiliation: Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: José Miguel
authors.initials: JM
authors.lastname: Ortega
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: André
authors.initials: A
authors.lastname: Oliveira
authors.affiliation: Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
authors.forename: M Fátima
authors.initials: MF
authors.lastname: Leite
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D054357:Chemokine CXCL10 / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000235:genetics; D064726:Triple Negative Breast Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D015544:Inositol 1,4,5-Trisphosphate