Sinais nucleares de cálcio dependentes de inositol 1,4,5-trisfosfato são necessários para a angiogênese e migração celular em tumores de mama triplo-negativos

• Ano de defesa: 2016
• Autor(a) principal: Erika Sousa Guimarães
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Cálcio nuclear; angiogênese; câncer de mama triplo-negativo; migração; Cálcio; Neoplasias de mama triplo negativas; Movimento celular; Sinalização do cálcio; Medicina; Inibidores de angiogênese
• Link de acesso: http://hdl.handle.net/1843/BUBD-AW2FZB

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 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 breast cancer angiogenesis and cell migration and can be considered as a promising strategic target for triple negative breast cancer therapy.