E2F1-Associated Purine Synthesis Pathway Is a Major Component of the MET-DNA Damage Response Network.

Unlabelled: Various lines of investigation support a signaling interphase shared by receptor tyrosine kinases and the DNA damage response. However, the underlying network nodes and their contribution to the maintenance of DNA integrity remain unknown. We explored MET-related metabolic pathways in which interruption compromises proper resolution of DNA damage.

A DNA-PK phosphorylation site on MET regulates its signaling interface with the DNA damage response.

The DNA damage response (DDR) is intertwined with signaling pathways downstream of oncogenic receptor tyrosine kinases (RTKs). To drive research into the application of targeted therapies as radiosensitizers, a better understanding of this molecular crosstalk is necessary. We present here the characterization of a previously unreported MET RTK phosphosite, Serine 1016 (S1016) that represents a potential DDR-MET interface.

Deciphering MET-dependent modulation of global cellular responses to DNA damage by quantitative phosphoproteomics.

Increasing evidence suggests that interference with growth factor receptor tyrosine kinase (RTK) signaling can affect DNA damage response (DDR) networks, with a consequent impact on cellular responses to DNA-damaging agents widely used in cancer treatment. In that respect, the MET RTK is deregulated in abundance and/or activity in a variety of human tumors. Using two proteomic techniques, we explored how disrupting MET signaling modulates global cellular phosphorylation response to ionizing radiation (IR).

MET targeting: time for a rematch.

MET, the receptor tyrosine kinase (RTK) for hepatocyte growth factor, is a proto-oncogene involved in embryonic development and throughout life in homeostasis and tissue regeneration. Deregulation of MET signaling has been reported in numerous malignancies, prompting great interest in MET targeting for cancer therapy. The present review offers a summary of the biology of MET and its known functions in normal physiology and carcinogenesis, followed by an overview of the most relevant MET-targeting strategies and corresponding clinical trials, highlighting both past setbacks and promising future prospects.