[No authors listed]
Immunoglobulinâlike transcript (ILT) 4, a negative regulator of immune response in allograft rejection, autoimmunity and infectious diseases, has recently been determined to serve important roles in tumor development. In the present study, the coâexpression of ILT4 and human leukocyte antigenâG (HLAâG) in tissues of human primary colorectal cancer (CRC) was revealed, and its association with older age, advanced stage, regional lymph node involvement and poor overall survival time was identified. In CRC cell lines, ILT4 and HLAâG coâexpression and their autocrine regulation was demonstrated. ILT4 interference affected HLAâG expression and regulated the cell proliferation, invasion and migration of CRC. HLAâG fusion protein treatment also increased ILT4 expression in a doseâdependent manner, thereby activating protein kinase B (AKT) and extracellular signalâregulated kinase (ERK) signaling, and facilitating the proliferation, migration and invasion of CRC cells. Additionally, the AKT and ERK activation, and CRC cell malignant characteristics induced by HLAâG may be suppressed by blocking ILT4. The present results indicated that the interaction of ILT4 and its ligand HLAâG promotes CRC progression through AKT and ERK signal activation, providing a novel strategy of blocking ILT4/HLAâG for the treatment of CRC.
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