Jianhua Luo
University of Pittsburgh School of Medicine, USA
Title: Novel ectopic signaling of MAN2A1-FER fusion protein
Biography
Biography: Jianhua Luo
Abstract
Cancer remains one of the most lethal diseases for human. Oncogenic fusion gene is one of the fundamental mechanisms driving the progression of human cancers. MAN2A1-FER, a fusion gene between the mannosidase domain of MAN2A1 and tyrosine kinase domain of FER, was found in 6 different types of human malignancies. MAN2A1-FER fusion translocated FER domain from cytoplasm to golgi apparatus, and led to phosphorylation of N-terminus of EGFR and activation of EGFR signaling pathway. Expression of MAN2A1-FER generated dramatic increase of growth and invasion of cancers, while removal of MAN2A1-FER through knockout generated significant lower level of growth and metastasis. The presence of MAN2A1-FER increased the sensitivity of human cancers to FER kinase inhibitor crizotinib or EGFR kinase inhibitor canertinib. Hydrodynamic tail-vein injection of MAN2A1-FER gene resulted in rapid development of liver cancer in mice with somatic Pten deletion. Taken together, we concluded that MAN2A1-FER fusion gene is one of the key drivers for human cancer development.