Activation of GLI1 which is the transcription factor through which the Hh signaling is mediated has been shown to be a key step in the initiation of the tumorigenic program leading to BCC. We recently showed that GLI1 was also regulated by the insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) at the post-transcriptional level. We showed that IGF2BP1 which is a direct target of the Wnt/β-catenin signaling was critical in Wnt-dependent regulation of GLI. We also observed that the regulation of GLI1 by the Hh upstream signal was IGF2BP1-dependent. We hypothesized that inhibition of IGF2BP1 will reduce GLI1 expression and activity thereby preventing BCC development. To test our hypothesis, we determined the effects of IGF2BP1 inhibition on the growth of BCC cells UW-BCC1 xenografts. 2 million UW-BCC1 cells were injected subcutaneously in the back of 30 immunocompromised mice (Foxn1nu), and they were fed doxycycline supplemented chow. Tumor growth was monitored weekly for eight weeks. Knockdown of IGF2BP1 in UW-BCC1 cells significantly reduced tumor growth in xenograft mice compared to controls (P<0.05). We also generated a skin specific IGF2BP1 knockout mouse model in a BCC background (Ptch1tm1Mps/J) using the Cre/LoxP system. Experimental mice (IGF2BP1-loxP+/-; K5-cre-ERT2+/-; Ptch1+/- or IGF2BP1-loxP-/-; K5-cre-ERT2+/-; Ptch1+/-) received 75mg of tamoxifen/kg for five days to inhibit IGF2BP1. They were subsequently exposed to 240 mJ/cm2 UVB irradiation, three times a week for 44 weeks. Inhibition of IGF2BP1 significantly reduced tumor development compared to the control mice (P<0.05). IGF2BP1 appears to contribute to BCC development and might represents a novel target in the treatment of basal cell carcinoma.

ESDR427 - Inhibiting insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) reduces tumor development in the basal cell carcinoma mouse model PTCH+/-

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.