PMC:4307189 / 38983-40625 JSONTXT

{"project":"2_test","denotations":[{"id":"25599599-22372504-14868146","span":{"begin":543,"end":545},"obj":"22372504"},{"id":"25599599-15578921-14868147","span":{"begin":546,"end":548},"obj":"15578921"},{"id":"25599599-22372504-14868148","span":{"begin":637,"end":639},"obj":"22372504"},{"id":"25599599-15578921-14868148","span":{"begin":637,"end":639},"obj":"15578921"},{"id":"25599599-23547709-14868148","span":{"begin":637,"end":639},"obj":"23547709"},{"id":"25599599-20651349-14868148","span":{"begin":637,"end":639},"obj":"20651349"},{"id":"25599599-23547709-14868149","span":{"begin":769,"end":771},"obj":"23547709"},{"id":"25599599-20651349-14868150","span":{"begin":772,"end":774},"obj":"20651349"},{"id":"25599599-23547709-14868151","span":{"begin":1024,"end":1026},"obj":"23547709"},{"id":"25599599-22439932-14868152","span":{"begin":1268,"end":1270},"obj":"22439932"},{"id":"25599599-19928349-14868153","span":{"begin":1377,"end":1379},"obj":"19928349"},{"id":"25599599-12711691-14868154","span":{"begin":1380,"end":1382},"obj":"12711691"},{"id":"25599599-3349449-14868155","span":{"begin":1504,"end":1506},"obj":"3349449"},{"id":"25599599-23258168-14868156","span":{"begin":1574,"end":1576},"obj":"23258168"},{"id":"25599599-22610277-14868157","span":{"begin":1638,"end":1640},"obj":"22610277"}],"text":"Cross-talk between EGFR/ErbB and Wnt signaling\nWe found MDM2:APC (in Reactome and WikiPathway), KIT:CDC73 (in Reactome), MDM2:CDC73 (in Reactome), CBL:APC (in Reactome and KEGG), PDGFRA:APC (in Reactome), and CBL:CDC73 (in Reactome), AKT2:APC (in KEGG), AKT2:TP53 (in KEGG), and TP53:APC (in WikiPathway) as putative drug-resistant cross-talks between EGFR/ErbB and Wnt signaling pathways. Deregulation of the Wnt/ β-catenin signaling pathway plays a critical role in various cancers including breast, colorectal, pancreatic and colon cancer [47,48], and its association with drug-resistance has been studied by several research groups [47-50]. Recently, it has been reported that resistant cell lines exhibited increased Wnt signaling in both breast and colon cancer [49,50]. Loh et al. showed that genes in the Wnt signaling pathway, in both the β-catenin dependent (AXIN2, MYC, CSNK1A1) and the independent arms (ROR2, JUN), were up-regulated in cell lines resistant to tamoxifen compared to the parental MCF7 cell line [49]. Furthermore, ROR1, a constituent gene of Wnt signaling pathway, plays a sustainer role in EGFR-mediated prosurvival signaling in lung adenocarcinoma via signaling cross-talk and was therefore reported to be a potential therapeutic target [51]. APC and MDM2 in the MDM2:APC cross-talk are both tumor suppressors; they co-regulate DNA polymerase- β [52,53] which is reported to be hyper-activated in a cis-diamminedichloroplatinum(II) resistant P388 murine leukemia cell line [54]. Again, β-catenin whose stability is negatively regulated by APC [55], confers resistance to PI3K/Akt inhibitors in colon cancer [56]."}