Golgi protein 73 activation of MMP-13 promotes hepatocellular carcinoma cell invasion

// Di Jin 1* , Jun Tao 2* , Dan Li 3 , Yanan Wang 2 , Li Li 2 , Zhongdong Hu 4 , Zhenzhen Zhou 5 , Xiuli Chang 6 , Chunfeng Qu 6 and Hongbing Zhang 1,2 1 Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China 2 State Key Laboratory of Medical Molecular Biology, Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China 3 Cell Engineering Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China 4 Modern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China 5 Department of Physiology, Dalian Medical University, Dalian, China 6 State Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences, Beijing, China * These authors have contributed equally to this work Correspondence to: Hongbing Zhang, email: // Keywords : GP73, matrix metalloproteinase-13, hepatocellular carcinoma, invasion Received : March 09, 2015 Accepted : August 23, 2015 Published : September 10, 2015 Abstract Golgi Protein 73 (GP73) is a serum biomarker for hepatocellular carcinoma (HCC), however its role in HCC is not clear. We report that GP73 promotes cell invasion, the hallmark of malignancy, through the upregulation of matrix metalloproteinase-13 (MMP-13). GP73 enhances MMP-13 expression through cAMP responsive element binding protein (CREB)-mediated transcription activation. Levels of GP73 and MMP-13 are increased and positively correlated in human HCC tissues. Augmented MMP-13 potentiates HCC cell metastasis. Thus, the GP73-CREB-MMP-13 axis potentiates cancer cell invasion and may be a target for HCC treatment.