Altered receptor tyrosine kinase (RTK) activity has long been recognized as a key source of pro-mitotic and pro-survival signals that support the proliferation of cancer cells. The RTK EphA2 is particularly known to be overexpressed and to contribute to tumorigenic signaling in lung cancer. However, the downstream signaling pathways that transduce EphA2 signaling into biological outcomes are not well understood. Here, Song and colleagues identify phospholipase Cγ1 (PLCγ1) Y783 as a key phosphorylation substrate and crucial signaling mediator downstream of EphA2. Perturbations of EphA2 and PLCγ1 expression and/or activity revealed that this axis was necessary for tumor proliferation in multiple models. Taken together, the data provide a foundation for developing interventions that target EphA2-PLCγ1 signaling for therapeutic benefit.
Heterotypic interactions between the tumor cells and the stromal compartment play a key role in guiding the development of tumor development and metastasis. Here, Hanley and colleagues report a dynamic regulatory feedback...