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Inositol 1, 4, 5-trisphosphate-dependent nuclear calcium signals regulate angiogenesis and cell motility in triple negative breast cancer

2017; Public Library of Science; Volume: 12; Issue: 4 Linguagem: Inglês

10.1371/journal.pone.0175041

ISSN

1932-6203

Autores

Erika S. Guimarães, Rodrigo Matta Machado, Matheus de Castro Fonseca, Andressa França, Juliana Carvalho‐Tavares, Ana Cândida Araújo e Silva, Brígida Gomes Almeida, Puebla Cassini, Bárbara Hissa, Luciana E. Drumond, Carlos Alberto Gonçalves, Gabriel da Rocha Fernandes, Marina De Brot, Márcio Flávio Dutra Moraes, Lucíola S. Barcelos, José Miguel Ortega, A. G. de Oliveira, M. Fátima Leite,

Tópico(s)

Wnt/β-catenin signaling in development and cancer

Resumo

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.

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