Role of FGFR2b in the crosstalk between autophagy and differentiation: involvement of JNK signaling

The FGFR2b is a receptor tyrosine kinase expressed exclusively in epithelial cells. We previously demonstrated that FGFR2b induces autophagy and that this process is required for the triggering of FGFR2b-mediated keratinocytes early differentiation. However, the molecular mechanisms regulating this interplay remain to be elucidated. Since we have also recently shown that JNK1 signaling is involved in FGFR2b-induced autophagy and a possible role of JNK pathway in epidermal differentiation has been suggested but it is still debated, here we investigated the crosstalk between FGFR2b-mediated autophagy and differentiation focusing on the downstream JNK signaling. Biochemical, molecular and immunofluorescence approaches in 2D keratinocyte cultures and 3D organotypic skin equivalents confirmed that FGFR2b overexpression increased both autophagy and early differentiation. The use of FGFR2b substrate inhibitors and the silencing of JNK1 highlighted that this signaling is required not only for autophagy but also for the triggering of early differentiation. In contrast, ERK1/2 pathway did not appear to be involved in the two processes and AKT signaling, whose activation contributes to the FGFR2b-mediated onset of keratinocyte differentiation, was not required for the triggering of autophagy. Overall, our results point to JNK1 as a signaling hub that regulates the interplay between FGFR2b-induced autophagy and differentiation.