Abstract:
:Drug development efforts against cancer are often hampered by the complex properties of signaling networks. Here we combined the results of an RNAi screen targeting the cellular signaling machinery, with graph theoretical analysis to extract the core modules that process both mitogenic and oncogenic signals to drive cell cycle progression. These modules encapsulated mechanisms for coordinating seamless transition of cells through the individual cell cycle stages and, importantly, were functionally conserved across different cancer cell types. Further analysis also enabled extraction of the core signaling axes that progressively guide commitment of cells to the division cycle. Importantly, pharmacological targeting of the least redundant nodes in these axes yielded a synergistic disruption of the cell cycle in a tissue-type-independent manner. Thus, the core elements that regulate temporally distinct stages of the cell cycle provide attractive targets for the development of multi-module-based chemotherapeutic strategies.
journal_name
Genome Resjournal_title
Genome researchauthors
Jailkhani N,Ravichandran S,Hegde SR,Siddiqui Z,Mande SC,Rao KVdoi
10.1101/gr.116145.110subject
Has Abstractpub_date
2011-12-01 00:00:00pages
2067-81issue
12eissn
1088-9051issn
1549-5469pii
gr.116145.110journal_volume
21pub_type
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