He Huang1,2, Jun Zhang1, Fei Ling1, Yuhong Huang1, Min Yang1, Yao Zhang1, Yuanyi Wei1, Qingqing Zhang1, Honghai Wang1, Lin Song3, Ying Wu1, Jiayu Yang1, Jianwu Tang4. 1. Department of Pathology, College of Basic Medical Sciences, Dalian Medical University, 9 W. Lushun South Road, Dalian, 116044, Liaoning, China. 2. Department of Pathology, Tangshan People's Hospital, 65 Shengli Road, Tangshan, 063001, Hebei, China. 3. Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, 94158, USA. 4. Department of Pathology, College of Basic Medical Sciences, Dalian Medical University, 9 W. Lushun South Road, Dalian, 116044, Liaoning, China. Jwtang_53@sina.cn.
Abstract
BACKGROUND: Leptin Receptor (LEPR) has been suggested to have several roles in cancer metastasis. However, the role of LEPR and its underlying mechanisms in lymphatic metastasis of hepatocarcinoma have not yet been studied. METHODS: We performed bioinformatics analysis, qRT-PCR, western blotting, immunohistochemistry, immunofluorescence, enzyme-linked immunosorbent, coimmunoprecipitation assays and a series of functional assays to investigate the roles of LEPR in hepatocellular carcinoma. RESULTS: We discovered that LEPR was highly expressed in liver cancer tissues, and the expression of LEPR in Hca-F cells was higher than that in Hca-P cells. Furthermore, LEPR promotes the proliferation, migration and invasion and inhibits the apoptosis of hepatocarcinoma lymphatic metastatic cells. Further studies indicated that LEPR interacts with ANXA7. Mechanistically, LEPR regulated ERK1/2 and JAK2/STAT3 expression via ANXA7 regulation. CONCLUSIONS: These findings unveiled a previously unappreciated role of LEPR in the regulation of lymphatic metastatic hepatocellular carcinoma, assigning ANXA7-LEPR as a promising therapeutic target for liver cancer treatments.
BACKGROUND:Leptin Receptor (LEPR) has been suggested to have several roles in cancer metastasis. However, the role of LEPR and its underlying mechanisms in lymphatic metastasis of hepatocarcinoma have not yet been studied. METHODS: We performed bioinformatics analysis, qRT-PCR, western blotting, immunohistochemistry, immunofluorescence, enzyme-linked immunosorbent, coimmunoprecipitation assays and a series of functional assays to investigate the roles of LEPR in hepatocellular carcinoma. RESULTS: We discovered that LEPR was highly expressed in liver cancer tissues, and the expression of LEPR in Hca-F cells was higher than that in Hca-P cells. Furthermore, LEPR promotes the proliferation, migration and invasion and inhibits the apoptosis of hepatocarcinoma lymphatic metastatic cells. Further studies indicated that LEPR interacts with ANXA7. Mechanistically, LEPR regulated ERK1/2 and JAK2/STAT3 expression via ANXA7 regulation. CONCLUSIONS: These findings unveiled a previously unappreciated role of LEPR in the regulation of lymphatic metastatic hepatocellular carcinoma, assigning ANXA7-LEPR as a promising therapeutic target for liver cancer treatments.
Authors: Lin Song; Jun Mao; Jun Zhang; Mohammed Mohammed Ibrahim; Lian-Hong Li; Jian-Wu Tang Journal: Biomed Pharmacother Date: 2013-12-02 Impact factor: 6.529
Authors: Stephanie O Dudzinski; Jackie E Bader; Kathryn E Beckermann; Kirsten L Young; Rachel Hongo; Matthew Z Madden; Abin Abraham; Bradley I Reinfeld; Xiang Ye; Nancie J MacIver; Todd D Giorgio; Jeffrey C Rathmell Journal: J Immunol Date: 2021-11-12 Impact factor: 5.426