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. Author manuscript; available in PMC: 2012 Dec 27.
Published in final edited form as: Nature. 2012 Oct 24;491(7424):399–405. doi: 10.1038/nature11547

Figure 2. SLIT/ROBO signalling in pancreatic ductal adenocarcinoma.

Figure 2

a, SLIT/ROBO signalling normally enhances β-catenin complex formation with E-cadherin and suppresses WNT signalling activity. Loss of ROBO1/2 signalling promotes stabilization of β-catenin, which decreases E-cadherin complex formation and cell adhesion and augments WNT signalling activity through increased nuclear translocation of β-catenin. In addition, SLIT/ROBO signalling can downregulate MET signalling activity; loss of ROBO signalling activity promotes MET signalling downstream and may have an impact on therapeutic strategies aimed at inhibiting MET activity at the receptor level. (Adapted from ref. 20.) Aberrations in SLIT2 and/or ROBO1/2 affected 23% of patients (6% mutated with 1 patient showing mutations in both SLIT2 and ROBO2), with 18% demonstrating CNV corresponding to loss of the gene. b, c, High expression of SLIT receptor ROBO2 was associated with a better prognosis (b), and high expression of ROBO3, an inhibitor of ROBO2, showed an inverse relationship, with high levels associated with poor survival (c). HR, hazard ratio.