A combined RNAi and SILAC approach to characterize tyrosine kinase-regulated proteome in breast cancer

Tyrosine kinases are important players in cancer progression and are considered as good therapeutic targets. Knocking down the multiple kinases in cancer and studying the consequences has been done before. But in a new study published in Molecular and Cellular Proteomics, they took this to a whole new level by silencing 65 tyrosine kinases in breast cancer cell lines and studying the proteome using a SILAC-based approach and an Orbitrap Velos mass spectrometer.

The authors identified 10 signaling clusters in breast cancers and potential markers of drug sensitivity and resistance in breast cancer. The clusters also showed correlation with different breast cancer subtypes. In addition, the data revealed redundancy in signaling, explaining why tyrosine kinases can be sometimes ineffective because the cancers can proliferate through alternate signaling routes that are not blocked therapeutically.