JAML overexpressed in colorectal cancer promotes tumour proliferation by activating the PI3K-AKT-mTOR signalling pathway

Abstract

Abstract The expression and biological function of junctional adhesion molecule-like protein (JAML) in colorectal cancer (CRC) remain unclear. Paraffin tissue samples from 50 cases of CRC were collected to determine the expression of JAML. JAML was overexpressed or knock-down in CRC cells to evaluated the proliferation, migration and invasion in vitro and in vivo. Western-blot and others were applied to explore the mechanisms. The study showed that JAML was highly expressed within cancer tissues in 50% (25/50) of patients with CRC, and was correlated with higher TNM stage (p < 0.05). Patients of JAML-high group had poorer overall survival compared to JAML-low group (p = 0.0362, HR = 0.4295, 95% CI of 0.1908–0.9667). The tumour infiltrating lymphocytes (TILs) was lower in the JAML-high group than in the JAML-low group (p < 0.05). Overexpression of JAML promoted the proliferation, migration, and invasion of CRC by activating the PI3K-AKT-mTOR signalling pathway both in vitro and in vivo. TILs were reduced in JAML-high tumour tissues by decreasing chemokines such as CCL20 and CXCL9/10/11. Our study identified JAML, a potentially ideal target that is specifically highly expressed in CRC tissues, which promoted tumour proliferation, impaired T-lymphocytes infiltration, provided a promising therapeutic strategy for patients with CRC.

Keywords

• Junctional adhesion molecule-like protein (JAML)
• Colorectal cancer
• Proliferation
• Targeted therapy
• T-cell infiltration