Clinical relevance of integrin alpha 4 in gastrointestinal stromal tumours

Abstract

The molecular mechanisms for the dissemination and metastasis of gastrointestinal stromal tumours (GIST) are incompletely understood. The purpose of the study was to investigate the clinical relevance of integrin alpha 4 (ITGA4) expression in GIST. GIST transcriptomes were first compared with transcriptomes of other types of cancer and histologically normal gastrointestinal tract tissue in the MediSapiens in silico database. ITGA4 was identified as an unusually highly expressed gene in GIST. Therefore, the effects of ITGA4 knock‐down and selective integrin alpha 4 beta 1 (VLA‐4) inhibitors on tumour cell proliferation and invasion were investigated in three GIST cell lines. In addition, the prognostic role of ITGA4 expression in cancer cells was investigated in a series of 147 GIST patients with immunohistochemistry. Inhibition of ITGA4‐related signalling decreased GIST cell invasion in all investigated GIST cell lines. ITGA4 protein was expressed in 62 (42.2%) of the 147 GISTs examined, and expression was significantly associated with distant metastases during the course of the disease and several adverse prognostic features. Patients whose GIST expressed strongly ITGA4 had unfavourable GIST‐specific survival and overall survival compared to patients with low or no ITGA4 expression. Taken together, ITGA4 is an important integrin in the molecular pathogenesis of GIST and may influence their clinical behaviour.

DNA Methylation Changes in Human Papillomavirus-Driven Head and Neck Cancers

“…Many other non-HPV-driven cancer studies have reported similar findings [111,112]. The gene positioned at 2q31.3 encodes for alpha 4 peptides, which function as crucial integrins in association with beta 1 or beta 7 peptides [113,114]. These integrins mediate cellular adhesion, migration, and signalling [115].…”

Chitosan oligosaccharides packaged into rat adipose mesenchymal stem cells-derived extracellular vesicles facilitating cartilage injury repair and alleviating osteoarthritis

“…However, few reports have shown the roles of ITGA4 , BAD , PPP2R3A , CPT1B , ACACB , CACNA1S , CACNG1 , and MAPK12 in cartilage injury repair. ITGA4 encodes a member of the integrin α chain family, and its high level is associated with many diseases, such as chronic lymphocytic leukemia [ 55 ], gastrointestinal stromal tumors [ 56 ] and colorectal cancer [ 57 ]. BAD plays a key role in mitochondria-dependent apoptosis, and its inactivation contributes to the development of rheumatoid arthritis by conferring apoptosis resistance in synovial sub lining macrophages [ 58 ].…”

Molecular Delivery of Cytotoxic Agents via Integrin Activation

“… RGD or cRGDs are the main peptides employed in these conjugates; however, in the literature much more integrin ligands have been developed, so other molecules, especially those more selective, should be investigated as targeting moieties. Some integrins are going to emerge as interesting targets in cancer cells and could be investigated, such as α 4 β 1 integrin in multiple myeloma resistant to bortezomib, β 7 [ 118 , 119 , 120 ], α v β 6 [ 121 ], and α 3 β 1 integrins [ 122 ]. Application of selective integrin agonists could enhance a more selective internalization of the conjugates [ 123 ].…”

“…Some integrins are going to emerge as interesting targets in cancer cells and could be investigated, such as α 4 β 1 integrin in multiple myeloma resistant to bortezomib, β 7 [ 118 , 119 , 120 ], α v β 6 [ 121 ], and α 3 β 1 integrins [ 122 ].…”