Dataset Information

Disabled-1 is down-regulated in clinical breast cancer and regulates cell apoptosis through NF-?B/Bcl-2/caspase-9.

ABSTRACT: Disabled-1 (Dab1) is best known as an adaptor protein regulating neuron migration and lamination during development. However, the exact function of Dab1 in breast cancer is unknown. In this study, we examined the expression of Dab1 in 38 breast cancer paraffin sections, as well as 60 paired frozen breast cancer and their adjacent tissues. Our results showed that Dab1 was reduced in breast cancer, and its compromised expression correlated with triple negative breast cancer phenotype, poor differentiation, as well as lymph node metastasis. Functional analysis in breast cancer cell lines demonstrated that Dab1 promoted cell apoptosis, which, at least partially, depended on its regulation of NF-?B/Bcl-2/caspase-9 pathway. Our study strongly suggests that Dab1 may be a potential tumour suppressor gene in breast cancer.

SUBMITTER: Cao RJ

PROVIDER: S-EPMC6349202 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Disabled-1 is down-regulated in clinical breast cancer and regulates cell apoptosis through NF-κB/Bcl-2/caspase-9.

Cao Rang-Juan RJ Li Kai K Xing Wan-Ying WY Du Shuang S Li Qiang Q Zhu Xiao-Juan XJ Cui Shu-Sen SS

Journal of cellular and molecular medicine 20181128 2

Disabled-1 (Dab1) is best known as an adaptor protein regulating neuron migration and lamination during development. However, the exact function of Dab1 in breast cancer is unknown. In this study, we examined the expression of Dab1 in 38 breast cancer paraffin sections, as well as 60 paired frozen breast cancer and their adjacent tissues. Our results showed that Dab1 was reduced in breast cancer, and its compromised expression correlated with triple negative breast cancer phenotype, poor differe ...[more]

PMID: 30484953

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Project description:BackgroundSpecificity protein (Sp) 1 mediates the transcription of a large number of constitutive genes encoding physiological mediators. NF-κB mediates the expression of hundreds of inducible genes encoding pathological mediators. Crosstalk between Sp1 and NF-κB pathways could be pathophysiologically significant, but has not been studied. This study examined the crosstalk between the two pathways and defined the role of NF-κB signaling in LPS-induced down-regulation of Sp1 activity.Methods and main findingsChallenge of wild type mice with samonelia enteritidis LPS (10 mg/kg, i.p.) down-regulated Sp1 binding activity in lungs in a time-dependent manner, which was concomitantly associated with an increased NF-κB activity. LPS down-regulates Sp1 activity by inducing an LPS inducible Sp1-degrading enzyme (LISPDE) activity, which selectively degrades Sp1 protein, resulting in Sp1 down-regulation. Blockade of NF-κB activation in mice deficient in NF-κB p50 gene (NF-κB-KO) suppressed LISPDE activity, prevented Sp1 protein degradation, and reversed the down-regulation of Sp1 DNA binding activity and eNOS expression (an indicator of Sp1 transactivation activity). Inhibition of LISPDE activity using a selective LISPDE inhibitor mimicked the effects of NF-κB blockade. Pretreatment of LPS-challenged WT mice with a selective LISPDE inhibitor increased nuclear Sp1 protein content, restored Sp1 DNA binding activity and reversed eNOS protein down-regulation in lungs. Enhancing tissue level of Sp1 activity by inhibiting NF-κB-mediated Sp1 down-regulation increased tissue level of IL-10 and decreased tissue level of TNF- αin the lungs.ConclusionsNF-κB signaling mediates LPS-induced down-regulation of Sp1 activity. Activation of NF-κB pathway suppresses Sp1 activity and Sp1-mediated anti-inflammatory signals. Conversely, Sp1 signaling counter-regulates NF-κB-mediated inflammatory response. Crosstalk between NF-κB and Sp1 pathways regulates the balance between pro- and anti-inflammatory cytokines.

Dataset Information

Disabled-1 is down-regulated in clinical breast cancer and regulates cell apoptosis through NF-?B/Bcl-2/caspase-9.

Publications

Disabled-1 is down-regulated in clinical breast cancer and regulates cell apoptosis through NF-κB/Bcl-2/caspase-9.

Similar Datasets

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