IGFBP7 Is Not Required for B-RAF-Induced Melanocyte Senescence

SummaryInduction of senescence permanently restricts cellular proliferation after oncogenic stimulation thereby acting as a potent barrier to tumor development. The relevant effector proteins may therefore be fundamental to cancer development. A recent study identified IGFBP7 as a secreted factor mediating melanocyte senescence induced by oncogenic B-RAF, which is found commonly in cutaneous nevi. In contrast to the previous report, we demonstrate that B-RAF signaling does not induce IGFBP7 expression, nor the expression of the IGFBP7 targets, BNIP3L, SMARCB1, or PEA15, in human melanocytes or fibroblasts. We also found no correlation between B-RAF mutational status and IGFBP7 protein expression levels in 22 melanoma cell lines, 90 melanomas, and 46 benign nevi. Furthermore, using a lentiviral silencing strategy we show that B-RAF induces senescence in melanocytes and fibroblasts, irrespective of the presence of IGFBP7. Therefore, we conclude that the secreted protein IGFBP7 is dispensable for B-RAFV600E-induced senescence in human melanocytes.

► Expression of activated B-RAF in human melanocytes induces p16INK4a but reduces p53 ► IGFBP7 expression does not correlate with B-RAF status in human metastatic melanomas ► IGFBP7 protein does not correlate with B-RAF status in human nevi or melanomas ► Oncogenic B-RAF initiates senescence in melanocytes/fibroblasts irrespective of IGFBP7