Genes co-amplified with ERBB2 or MET as novel potential cancer-promoting genes in gastric cancer

Abstract

Gastric cancer (GC), one of the most common cancers worldwide, has a high mortality rate due to limited treatment options. Identifying novel and promising molecular targets is a major challenge that must be overcome if treatment of advanced GC is to be successful. Here, we used comparative genomic hybridization and gene expression microarrays to examine genome-wide DNA copy number alterations (CNAs) and global gene expression in 38 GC samples from old and young patients. We identified frequent CNAs, which included copy number gains on chromosomes 3q, 7p, 8q, 20p, and 20q and copy number losses on chromosomes 19p and 21p. The most frequently gained region was 7p21.1 (55%), whereas the most frequently deleted region was 21p11.1 (50%). Recurrent highly amplified regions 17q12 and 7q31.1-7q31.31 harbored two well-known oncogenes: ERBB2 and MET. Correlation analysis of CNAs and gene expression levels identified CAPZA2 (co-amplified with MET) and genes GRB7, MIEN1, PGAP3, and STARD3 (co-amplified with ERBB2) as potential candidate cancer-promoting genes (CPGs). Public dataset analysis confirmed co-amplification of these genes with MET or ERBB2 in GC tissue samples, and revealed that high expression (except for PGAP3) was significantly associated with shorter overall survival. Knockdown of these genes using small interfering RNA led to significant suppression of GC cell proliferation and migration. Reduced GC cell proliferation mediated by CAPZA2 knockdown was attributable to attenuated cell cycle progression and increased apoptosis. This study identified novel candidate CPGs co-amplified with MET or ERBB2, and suggests that they play a functional role in GC.

The HMGB1-2 Ovarian Cancer Interactome. The Role of HMGB Proteins and Their Interacting Partners MIEN1 and NOP53 in Ovary Cancer and Drug-Response

“…References supporting the scheme are indicated for each protein as follows. AKIP1 [ 56 , 57 , 58 , 59 , 60 ], BCCIP [ 61 , 62 ], COMMD1 [ 63 , 64 , 65 ], C1QA [ 66 ], DAG1 [ 67 ], KRT7 [ 68 ], MALAT1 [ 24 , 69 , 70 ], MIEN1 [ 55 , 71 , 72 ], NOP53 [ 73 , 74 , 75 ], PCBP1 [ 76 , 77 , 78 ], RLP29 [ 79 , 80 ], ROCK1 [ 38 , 81 , 82 , 83 , 84 , 85 , 86 ], RSF1 [ 47 , 48 , 87 , 88 ], TGM2 [ 89 , 90 ], UHRF2 [ 91 , 92 ], U2AF1 [ 93 ], ZNF668 [ 94 , 95 ], ZRF [ 96 , 97 , 98 ].…”

Perspective Insight into Future Potential Fusion Gene Transcript Biomarker Candidates in Breast Cancer

“…Another important thing we should mention here is a very intriguing fact regarding the breast cancer fusion gene, ERBB2-GRB7 , which is a fusion between genes located in a close neighborhood in the human genome. Even though the fusion gene had been identified in breast cancer patients, the copy number amplicon (the one harboring the independent ERBB2 and GRB7 genes) had previously been reported in other cancer types, including gastric cancer [ 13 , 14 ]. In addition, the authors demonstrated that the co-amplification of those genes in the amplicons could result in simultaneous up-regulation in their expression and also might contribute to carcinogenesis in an orchestrated, cooperative, and synergistic manner for their oncogenic activities.…”

PIM1 accelerates prostate cancer cell motility by phosphorylating actin capping proteins

“…The third variant, beta 3, is a testis-specific isoform similar to alpha 3 [13]. Despite their importance in skeletal muscle, various functional roles have also been reported in other tissues, such as cardiac tissue, the nervous system and cancer [14][15][16][17][18][19][20][21].…”

“…The role of CPs in cancer has remained unclear due to contradictory results with different subunits. While the beta subunit has been reported to act as an oncogene, variable but mainly tumor suppressive roles have been suggested for the alpha subunits [17][18][19][20][21]. These opposite effects are surprising due to the heterodimeric mode of CP action.…”