JAML overexpression in tumour vascular endothelial cells promotes cancer proliferation via angiogenesis through VEGF signalling pathway activation

Abstract Angiogenesis is a crucial process in tumour growth and metastasis.Junctional adhesion molecule-like protein (JAML) plays a role in various tumours; however, its role in tumour angiogenesis remains unexplored. We collected colorectal cancer samples from Jinan Central Hospital, using immunofluorescence staining and cell lines for analysis. JAML effects were examined in mice, including vascular leakage and tumour characteristics. A range of assays, such as Western blot analysis, were utilised to obtain comprehensive data. Statistical analysis was conducted using GraphPad Prism version 8.0. Our findings indicate a significant upregulation of JAML in colorectal cancer tissues. Endothelial-specific knockout of JAML minimally impacted organ development, but effectively inhibited tumour growth through antiangiogenesis in multiple mouse tumour models. The deletion of JAML was observed to enhance T-lymphocyte infiltration within tumour tissues and facilitate vascular normalisation, evident from increased pericyte coverage and vessel perfusion. Conversely, the overexpression of JAML in endothelial cells during in vitro experiments was observed to enhance migration, invasion, proliferation, and tube formation in HUVECs. Mechanistically, endothelial JAML bounded to FAK/SRC to upregulate the expression of vascular endothelial growth factor (VEGFA) in vitro and in vivo. Our findings underscore the pivotal role of endothelial JAML/FAK/SRC/VEGFA signalling in tumour angiogenesis, positioning JAML as an ideal target for antiangiogenesis in cancer therapy. This study has the potential to provide valuable insights into the development of new therapeutic approaches, increase the effectiveness of existing treatments, and improve clinical outcomes for cancer patients.