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ADAM23 negatively modulates alpha(v)beta(3) integrin activation during metastasis
Newton V Verbisck1, Erico T Costa, Fabrício F Costa
1Laboratory of Molecular Biology and Genomics, Ludwig Institute for Cancer Research, São Paulo SP, Brazil.
Cancer Research
|June 25, 2009
Summary
ADAM23 gene silencing in breast tumors enhances alpha(v)beta(3) integrin activation, promoting cancer cell migration and metastasis. Silencing is linked to poorer survival, indicating ADAM23
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- ADAM23 gene silencing is observed in various tumors, correlating with breast tumor progression and metastasis.
- ADAM23 functions via its disintegrin domain, interacting specifically with alpha(v)beta(3) integrin.
- Activated alpha(v)beta(3) integrin expression promotes metastasis in tumors.
Purpose of the Study:
- To investigate if ADAM23 negatively modulates alpha(v)beta(3) integrin activation during metastatic progression.
- To explore the functional role of ADAM23 in breast cancer metastasis.
Main Methods:
- ADAM23 expression was reduced using short hairpin RNA in MDA-MB-435 cells.
- Cellular migration, adhesion, and pulmonary tumor cell arrest in mice were analyzed.
- ADAM23 gene promoter hypermethylation was assessed in 94 primary breast tumors.
Main Results:
- ADAM23 knockdown increased alpha(v)beta(3) integrin activation by 2- to 4-fold.
- ADAM23-deficient cells exhibited enhanced migration, adhesion, and pulmonary metastasis.
- ADAM23 gene silencing via hypermethylation correlated with reduced metastasis-free and disease-specific survival.
Conclusions:
- ADAM23 negatively regulates alpha(v)beta(3) integrin activation, thereby suppressing metastasis.
- ADAM23 acts as a tumor suppressor by inhibiting cancer cell migration and adhesion.
- ADAM23 silencing is an independent prognostic marker for poor outcomes in breast cancer patients.
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