What is it about?
The top-5 highly expressed and connected proteins (hub) HSP90AB1, CSNK2B, TK1, YWHAB and VIM are up-regulated in MDA-MB-231, a malignant cell of breast cancer. The expression of these proteins has been knocked down individually or together using siRNAs. The transfected cell lines were assessed for in vitro cell growth, colony formation, migration and invasion in transfected cell lines MDA-MB-231 of tripple negative, the non-invasive MCF-7 breast carcinoma and the non-tumoral mammary epithelial cell line MCF-10A. The knockdown of the top-5 upregulated connectivity hubs successfully inhibited the in vitro proliferation, colony formation, anchorage independence, migration and invasion in MDA-MB-231 cells; with minimal effects in the control transfected MDA-MB-231 cells or MCF-7 and MCF-10A cells.
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Why is it important?
Network-based strategies provided by systems biology were proven mathemtically to be effective for network disarticulation. The application of network theory to the inactivation of up-regulated hubs enabled to validate the mathematical inferences in vitro.
Perspectives
The strategy proposed is based on RNAi and is designed to minimize noxious secondary effects to patients; it enables to glimpse further developments in drug development and repositioning for solid tumor therapy. The selection of most relevant targets for a given tumor is expected to provide an optimized process for effective anti-metastatic drug cocktails in the context of precision therapy of triple-negative breast cancer.
Nicolas Carels
Oswaldo Cruz Foundation
Read the Original
This page is a summary of: Validation of a network-based strategy for the optimization of combinatorial target selection in breast cancer therapy: siRNA knockdown of network targets in MDA-MB-231 cells as an in vitro model for inhibition of tumor development, Oncotarget, August 2016, Impact Journals, LLC,
DOI: 10.18632/oncotarget.11055.
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