Decoding and targeting the molecular basis of MACC1-driven metastatic spread: Lessons from big data mining and clinical-experimental approaches. (February 2020)

• Record Type: Journal Article
• Authors: Budczies, Jan; Kluck, Klaus; Walther, Wolfgang; Stein, Ulrike
• Is Part Of: Seminars in cancer biology. Volume 60(2020)
• Page Start: 365
• Page End: 379
• Publication Date: 2020-02
• Subjects: AKT AKT serine/threonine kinase -- ALDH1 ALDH1A1, aldehyde dehydrogenase 1 family member A1 -- ALK anaplastic lymphoma kinase -- AP1 activator protein 1 -- AP2 activating protein 2 -- APC APC regulator of Wnt signaling pathway -- BCL2 B-cell lymphoma 2 apoptosis regulator -- CCL1 CC-chemokine ligand 1 -- CD44 CD44 molecule -- CD133 prominin 1 -- CESC cervical squamous cell carcinoma and endocervical adenocarcinoma -- circRNA circular RNA -- CDKN1A cyclin dependent kinase inhibitor 1 -- CNV copy number variation -- COAD colon adenocarcinoma -- CRC colorectal cancer -- CYR61 cysteine rich angiogenic inducer 61 -- DLC3 deleted in liver cancer 3 protein -- dMMR deficient mismatch repair -- EF hand helix-loop-helix structural domain -- ELF1 E74 like ETS transcription factor 1 -- ELK1 ETS transcription factor ELK1 -- EMT epithelial-mesenchymal transistion -- ERK extracellular signal-regulated kinase -- ETS2 ETS proto-oncogene 2 -- ETV4 ETS variant 4 -- FAS FAS cell surface death receptor -- FAK focal adhesion kinase, protein tyrosine kinase 2 -- FIGO International Federation of Gynecology and Obstetrics -- FDR false discovery rate -- FOXO4 forkhead box O4 -- GADD45A growth-arrest and DNA-damage inducible protein 45A -- GO gene ontology -- HCC hepatocellular carcinoma -- HGF hepatocyte growth factor -- HTS high throughput screens -- IBD inflammatory bowel disease -- KAI1 kangai 1, suppression of tumorigenicity 6 -- KICH kidney chromophobe cell cancer -- KISS1 KISS1 metastasis suppressor -- KIT KIT proto-oncogene, receptor tyrosine kinase -- lncRNA long non-coding RNA -- LNM lymph-node-metastasis -- LOPAC library of pharmacologically active compounds -- LUAD lung adenocarcinoma -- MAPK mitogen-activated protein kinase -- MACC1 metastasis-associated in colon cancer 1 -- MCL1 induced myeloid leukemia cell differentiation protein 1 -- MCT1 solute carrier family 16, member 1 (monocarboxylic acid transporter 1) -- MEK MAP2K1, mitogen-activated protein kinase kinase 1 -- MET MET proto-oncogene, receptor tyrosine kinase -- miRNA microRNA -- MMR mismatch repair -- MMP2 matrix metalloproteinase 2 -- MMP7 matrix metalloproteinase 7 -- MMP9 matrix metalloproteinase 9 -- MSigDB Molecular Signatures Database Broad Institute -- MYC MYC proto-oncogene, BHLH Transcription Factor -- Nanog Nanog homeobox -- NFE2L1 nuclear factor, erythroid 2 like 1 -- NFE2L2 nuclear factor, erythroid 2 like 2 -- NF-κB nuclear factor κB -- NM23-H1 NME1, nucleoside diphosphate kinase 1 -- NSCLC non-small cell lung cancer -- Oct4 POU5F1, POU class 5 homeobox 1 -- Orai1 ORAI calcium release-activated calcium modulator 1 -- PAAD pancreatic adenocarcinoma -- PCPG pheochromocytoma and paraganglioma -- PI3K phosphoinositide 3-kinase/serine-threonine kinase -- Pim-3 Pim-3 proto-oncogene, serine/threonine kinase -- PKB protein kinase B -- pMMR proficient mismatch repair -- PRAD prostate adenocarcinoma -- READ rectal adenocarcinoma -- RET RET proto-oncogene, tyrosine-protein kinase receptor -- RON MST1R macrophage stimulating 1 receptor -- ROS ROS1 proto-oncogene 1, ROS1, receptor tyrosine kinase -- S100A4 S100 calcium binding protein A4 -- SNP single nucleotide polymorphism -- SOX9 sex determining region Y (SRY)-Box 9 -- SOX17 sex determining region Y (SRY)-Box 17 -- Sp1 specificity protein 1 -- SPON2 spondin 2 -- STAD stomach adenocarcinoma -- STAT signal transducer and activator of transcription -- TCGA the cancer genome atlas -- TEAD1 TEA domain transcription factor 1 -- TF transcription factor -- THYM thymoma -- TNM tumor-node-metastasis -- TRAIL tumor necrosis factor related apoptosis inducing ligand -- TWIST twist family BHLH transcription factor -- TWISTNB TWIST neighbor -- ULK-1 Unc-51 like autophagy activating kinase -- UVM uveal melanoma -- VEGF-A vascular endothelial growth factor A -- VEGF-C vascular endothelial growth factor C -- VEGF-D vascular endothelial growth factor D -- VEGFR2 VEGF receptor 2 -- VM vasculogenic mimicry -- Wnt wingless-related integration site -- YB1 Y-box binding protein 1 -- ZEB1 zinc finger E-box binding homeobox 1 -- ZEB2 zinc finger E-box binding homeobox 2; MACC1 -- Big data analyses -- Cancer prognosis and prediction -- Biomarker combination -- Combinatorial therapy; Cancer -- Periodicals; Neoplasms -- Periodicals; Review Literature; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.semcancer.2019.08.010
• Languages: English
• ISSNs: 1044-579X

Abstract

Abstract: Metastasis remains the key issue impacting cancer patient survival and failure or success of cancer therapies. Metastatic spread is a complex process including dissemination of single cells or collective cell migration, penetration of the blood or lymphatic vessels and seeding at a distant organ site. Hundreds of genes involved in metastasis have been identified in studies across numerous cancer types. Here, we analyzed how the metastasis-associated gene MACC1 cooperates with other genes in metastatic spread and how these coactions could be exploited by combination therapies: We performed (i) a MACC1 correlation analysis across 33 cancer types in the mRNA expression data of TCGA and (ii) a comprehensive literature search on reported MACC1 combinations and regulation mechanisms. The key genes MET, HGF and MMP7 reported together with MACC1 showed significant positive correlations with MACC1 in more than half of the cancer types included in the big data analysis. However, ten other genes also reported together with MACC1 in the literature showed significant positive correlations with MACC1 in only a minority of 5 to 15 cancer types. To uncover transcriptional regulation mechanisms that are activated simultaneously with MACC1, we isolated pan-cancer consensus lists of 1306 positively and 590 negatively MACC1-correlating genes from the TCGA data and analyzed each of these lists for sharing transcription factor binding motifs in the promotor region. In these lists, binding sites for the transcription factors TELF1, ETS2, ETV4, TEAD1, FOXO4, NFE2L1, ELK1, SP1 and NFE2L2 were significantly enriched, but none of them except SP1 was reported in combination with MACC1 in the literature. Thus, while some of the results of the big data analysis were in line with the reported experimental results, hypotheses on new genes involved in MACC1-driven metastasis formation could be generated and warrant experimental validation. Furthermore, the results of the big data analysis can help to prioritize cancer types for experimental studies and testing of combination therapies.