Inhibition of DDR1-BCR signaling by nilotinib

Inhibition of DDR1-BCR signaling by nilotinib. Collagens from the extracellular matrix (ECM) microenvironment of colorectal cancer (CRC) cells induce the kinase activity of DDR1 (Discoïdin Domain Receptor tyrosine kinase 1), which phosphorylates its substrate BCR (Breakpoint Cluster Region) on the tyrosine 177 (Y177), subsequently disrupting BCR/β-catenin interaction. This signaling cascade results in an increased β-catenin/TCF (T-Cell Factor) nuclear activity leading to the expression of critical target genes (including MYC, JUN, FOSL1, CD44, LGR5, CCND1) necessary for cell invasion and metastatic development (left panel). Inhibition of DDR1 kinase activity with nilotinib decreases CRC cell invasion and metastasis by reducing this β-catenin pathway (right panel).
Inhibition of DDR1-BCR signaling by nilotinib
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Publication

DDR1 inhibition as a new therapeutic strategy for colorectal cancer. (2018) Audrey Sirvent, et al. Mol Cell Oncol. 2018;5(4):e1465882. Figure: F1.

Gene mentions


Organism Group Word Match Source NCBI Symbol NCBI ID
Homo sapiens Primates DDR1 DDR1 ncbigene_symbol DDR1 780
Homo sapiens Primates collagen COLLAGEN famplex_relations COL6A1 1291
Homo sapiens Primates collagen COLLAGEN famplex_relations COL6A2 1292
Homo sapiens Primates collagen COLLAGEN famplex_relations COL6A3 1293
Homo sapiens Primates collagen COLLAGEN famplex_relations COL6A5 256076
Homo sapiens Primates collagen COLLAGEN famplex_relations COL6A6 131873
Homo sapiens Primates collagen COLLAGEN famplex_relations COL7A1 1294
Homo sapiens Primates collagen COLLAGEN famplex_relations COL8A1 1295
Homo sapiens Primates collagen COLLAGEN famplex_relations COL8A2 1296
Homo sapiens Primates collagen COLLAGEN famplex_relations COL9A1 1297
Homo sapiens Primates collagen COLLAGEN famplex_relations COL9A2 1298
Homo sapiens Primates collagen COLLAGEN famplex_relations COL9A3 1299
Homo sapiens Primates collagen COLLAGEN famplex_relations COL10A1 1300
Homo sapiens Primates collagen COLLAGEN famplex_relations COL11A1 1301
Homo sapiens Primates collagen COLLAGEN famplex_relations COL11A2 1302
Homo sapiens Primates collagen COLLAGEN famplex_relations COL12A1 1303
Homo sapiens Primates collagen COLLAGEN famplex_relations COL13A1 1305
Homo sapiens Primates collagen COLLAGEN famplex_relations COL14A1 7373
Homo sapiens Primates collagen COLLAGEN famplex_relations COL15A1 1306
Homo sapiens Primates collagen COLLAGEN famplex_relations COL16A1 1307
Homo sapiens Primates collagen COLLAGEN famplex_relations COL17A1 1308
Homo sapiens Primates collagen COLLAGEN famplex_relations COL18A1 80781
Homo sapiens Primates collagen COLLAGEN famplex_relations COL19A1 1310
Homo sapiens Primates collagen COLLAGEN famplex_relations COL20A1 57642
Homo sapiens Primates collagen COLLAGEN famplex_relations COL21A1 81578
Homo sapiens Primates collagen COLLAGEN famplex_relations COL22A1 169044
Homo sapiens Primates collagen COLLAGEN famplex_relations COL23A1 91522
Homo sapiens Primates collagen COLLAGEN famplex_relations COL24A1 255631
Homo sapiens Primates collagen COLLAGEN famplex_relations COL25A1 84570
Homo sapiens Primates collagen COLLAGEN famplex_relations COL26A1 136227
Homo sapiens Primates collagen COLLAGEN famplex_relations COL27A1 85301
Homo sapiens Primates collagen COLLAGEN famplex_relations COL28A1 340267
Homo sapiens Primates collagen COLLAGEN famplex_relations COL1A1 1277
Homo sapiens Primates collagen COLLAGEN famplex_relations COL1A2 1278
Homo sapiens Primates collagen COLLAGEN famplex_relations COL4A1 1282
Homo sapiens Primates collagen COLLAGEN famplex_relations COL4A2 1284
Homo sapiens Primates collagen COLLAGEN famplex_relations COL4A3 1285
Homo sapiens Primates collagen COLLAGEN famplex_relations COL4A4 1286
Homo sapiens Primates collagen COLLAGEN famplex_relations COL4A5 1287
Homo sapiens Primates collagen COLLAGEN famplex_relations COL4A6 1288
Homo sapiens Primates collagen COLLAGEN famplex_relations COL5A1 1289
Homo sapiens Primates collagen COLLAGEN famplex_relations COL5A2 1290
Homo sapiens Primates collagen COLLAGEN famplex_relations COL5A3 50509
Homo sapiens Primates BCR BCR ncbigene_symbol BCR 613
Homo sapiens Primates BCR BCR ncbigene_synonym RN7SL263P 106480993
Homo sapiens Primates B-catenin CTNNB1 ncbigene_symbol CTNNB1 1499
Homo sapiens Primates TCF TCF ncbigene_synonym HNF4A 3172
Homo sapiens Primates JUN, JUN ncbigene_symbol JUN 3725
Homo sapiens Primates JUN, JUN famplex_relations JUNB 3726
Homo sapiens Primates JUN, JUN famplex_relations JUND 3727
Homo sapiens Primates MYC, MYC ncbigene_symbol MYC 4609
Homo sapiens Primates FOSLI,CD44, CD44 ncbigene_symbol CD44 960
Homo sapiens Primates CCND1. CCND1 ncbigene_symbol CCND1 595
Homo sapiens Primates LGR5,CCND1. LGR5 ncbigene_symbol LGR5 8549
Homo sapiens Primates FOS. FOS ncbigene_symbol FOS 2353
Homo sapiens Primates FOS. FOS famplex_relations FOSB 2354
Homo sapiens Primates FOS. FOS famplex_relations FOSL1 8061
Homo sapiens Primates FOS. FOS famplex_relations FOSL2 2355

Chemical mentions

Word Match MeSH Name ChEBI

Disease mentions

Word Match MeSH Name DOID
Cancer NA