Protein Kinase C alpha promotes tumor growth by initiating a feed-forward network involving miR15a and Cyclin E deregulation

3586 Protein Kinase C alpha (PKCα) has been implicated in cancer but the mechanism is unknown. Here we show that PKCα inhibitors decrease proliferation in squamous cell carcinoma (SCC) cell lines and inhibit growth of xenografted SCC tumors. PKCα enhances cyclin E protein expression and cyclinE/cdk2 complex formation required for DNA synthesis through inhibition of the microRNA, miR15a. Tissue analysis reveals positive and negative correlations between PKCα and cyclin E or miR15a, respectively; PKCα is also associated with head and neck cancer progression and poor prognosis. These results identify PKCα as a key regulator of tumor growth via activation of a feed-forward network leading to enhanced protein translation followed by increased transcription of E2F target genes that sustain the proliferative signal.