4.5 Article

Expression of nuclear XIAP associates with cell growth and drug resistance and confers poor prognosis in breast cancer

出版社

ELSEVIER
DOI: 10.1016/j.bbamcr.2020.118761

关键词

XIAP; Subcellular localization; Breast cancer; Drug resistance; Prognosis

资金

  1. Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ) [E-26/010.001808/2016]
  2. L'oreal-UNESCO-ABC Para Mulheres na Ciencia (L'oreal for women in science)
  3. Brazilian National Cancer Institute Ministry of Health (INCA-MS)
  4. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) Produtividade [304565/2016-4]
  5. FAPESP [2016/21310-6, 2016/25798-3]

向作者/读者索取更多资源

Evasion from apoptosis is one of the hallmarks of cancer. X-linked inhibitor of apoptosis protein (XIAP) is known to modulate apoptosis by inhibiting caspases and ubiquitinating target proteins. XIAP is mainly found at the cytoplasm, but recent data link nuclear XIAP to poor prognosis in breast cancer. Here, we generated a mutant form of XIAP with a nuclear localization signal (XIAP(NLs-C-term)) and investigated the oncogenic mechanisms associated with nuclear XIAP in breast cancer. Our results show that cells overexpressing XIAP(Delta RING) (RING deletion) and XIAP(NLs-C-term) exhibited XIAP nuclear localization more abundantly than XIAP(wild-type), Remarkably, overexpression of XIAP(NLs-C-term) but not XIAP(Delta RING), conferred resistance to doxorubicin and in- creased cellular proliferative capacity. Interestingly, Survivin and c-IAP1 expression were not associated with XIAP oncogenic effects. However, NF kappa B expression and ubiquitination of K63, but not K48 chains, were increased following XIAP(NLs-C-term) overexpression, pointing to nuclear signaling transduction. Consistently, multivariate analysis revealed nuclear, but not cytoplasmic XIAP, as an independent prognostic factor in hormone receptor-negative breast cancer patients. Altogether, our findings suggest that nuclear XIAP confers poor outcome and RING-associated breast cancer growth and chemoresistance.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据