In such ER-negative cells, enhanced PKCθ signaling also leads to the activation of ERK1/2 and Ste20-related proline-alanine-rich kinase (SPAK) as well as the phosphorylation of the Fos family protein Fra-1, thereby stabilizing it and regulating its role in the progression and maintenance of invasive breast cancer cell lines [137]. This evidence concerns the gene PRRT2 and breast carcinoma.